{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:36:39Z","timestamp":1793500599980,"version":"4.5.0"},"reference-count":271,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Mol Cell Biol"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1038\/s41580-026-01002-x","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:00:57Z","timestamp":1784649657000},"page":"763-780","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanisms, regulation and clinical relevance of necroptosis"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2504-4013","authenticated-orcid":false,"given":"Yuanxin","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-6176","authenticated-orcid":false,"given":"Huipeng","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3286-4968","authenticated-orcid":false,"given":"Daichao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"1002_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nchembio711","volume":"1","author":"A Degterev","year":"2005","unstructured":"Degterev, A. et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol. 1, 112\u2013119 (2005).","journal-title":"Nat. Chem. Biol."},{"key":"1002_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nchembio.83","volume":"4","author":"A Degterev","year":"2008","unstructured":"Degterev, A. et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol. 4, 313\u2013321 (2008). References 1 and 2 demonstrated the existence of necroptosis and the involvement of RIPK1 through their identification of Nec-1 as a small molecule RIPK1 inhibitor.","journal-title":"Nat. Chem. Biol."},{"key":"1002_CR3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/82732","volume":"1","author":"N Holler","year":"2000","unstructured":"Holler, N. et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat. Immunol. 1, 489\u2013495 (2000).","journal-title":"Nat. Immunol."},{"key":"1002_CR4","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.cell.2009.05.021","volume":"137","author":"S He","year":"2009","unstructured":"He, S. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100\u20131111 (2009).","journal-title":"Cell"},{"key":"1002_CR5","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.cell.2009.05.037","volume":"137","author":"YS Cho","year":"2009","unstructured":"Cho, Y. S. et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137, 1112\u20131123 (2009).","journal-title":"Cell"},{"key":"1002_CR6","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1126\/science.1172308","volume":"325","author":"DW Zhang","year":"2009","unstructured":"Zhang, D. W. et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325, 332\u2013336 (2009).","journal-title":"Science"},{"key":"1002_CR7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.cell.2011.11.031","volume":"148","author":"L Sun","year":"2012","unstructured":"Sun, L. et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213\u2013227 (2012). References 4, 5, 6 and 7 provided evidence demonstrating that RIPK3 and MLKL are core mediators of necroptosis.","journal-title":"Cell"},{"key":"1002_CR8","doi-asserted-by":"publisher","first-page":"5322","DOI":"10.1073\/pnas.1200012109","volume":"109","author":"J Zhao","year":"2012","unstructured":"Zhao, J. et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc. Natl Acad. Sci. USA 109, 5322\u20135327 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR9","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/cr.2013.91","volume":"23","author":"J Wu","year":"2013","unstructured":"Wu, J. et al. Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis. Cell Res. 23, 994\u20131006 (2013).","journal-title":"Cell Res."},{"key":"1002_CR10","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.immuni.2013.06.018","volume":"39","author":"JM Murphy","year":"2013","unstructured":"Murphy, J. M. et al. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39, 443\u2013453 (2013).","journal-title":"Immunity"},{"key":"1002_CR11","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.tcb.2016.06.004","volume":"26","author":"Y Dondelinger","year":"2016","unstructured":"Dondelinger, Y., Hulpiau, P., Saeys, Y., Bertrand, M. J. M. & Vandenabeele, P. An evolutionary perspective on the necroptotic pathway. Trends Cell Biol. 26, 721\u2013732 (2016).","journal-title":"Trends Cell Biol."},{"key":"1002_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.747737","volume":"12","author":"A Agueda-Pinto","year":"2021","unstructured":"Agueda-Pinto, A. et al. Convergent loss of the necroptosis pathway in disparate mammalian lineages shapes viruses countermeasures. Front. Immunol. 12, 747737 (2021).","journal-title":"Front. Immunol."},{"key":"1002_CR13","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.chom.2012.01.016","volume":"11","author":"JW Upton","year":"2012","unstructured":"Upton, J. W., Kaiser, W. J. & Mocarski, E. S. DAI\/ZBP1\/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11, 290\u2013297 (2012).","journal-title":"Cell Host Microbe"},{"key":"1002_CR14","doi-asserted-by":"publisher","first-page":"20054","DOI":"10.1073\/pnas.1116302108","volume":"108","author":"S He","year":"2011","unstructured":"He, S., Liang, Y., Shao, F. & Wang, X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc. Natl Acad. Sci. USA 108, 20054\u201320059 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR15","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.molcel.2014.03.003","volume":"54","author":"H Wang","year":"2014","unstructured":"Wang, H. et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell 54, 133\u2013146 (2014).","journal-title":"Mol. Cell"},{"key":"1002_CR16","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.it.2011.01.005","volume":"32","author":"DV Krysko","year":"2011","unstructured":"Krysko, D. V. et al. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol. 32, 157\u2013164 (2011).","journal-title":"Trends Immunol."},{"key":"1002_CR17","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/nature09852","volume":"471","author":"A Oberst","year":"2011","unstructured":"Oberst, A. et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature 471, 363\u2013367 (2011).","journal-title":"Nature"},{"key":"1002_CR18","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nature09857","volume":"471","author":"WJ Kaiser","year":"2011","unstructured":"Kaiser, W. J. et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471, 368\u2013372 (2011).","journal-title":"Nature"},{"key":"1002_CR19","doi-asserted-by":"publisher","first-page":"3874","DOI":"10.1016\/j.molcel.2025.09.007","volume":"85","author":"R Chen","year":"2025","unstructured":"Chen, R., Zou, J., Liu, J., Kang, R. & Tang, D. DAMPs in the immunogenicity of cell death. Mol. Cell 85, 3874\u20133889 (2025).","journal-title":"Mol. Cell"},{"key":"1002_CR20","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.chom.2010.03.006","volume":"7","author":"JW Upton","year":"2010","unstructured":"Upton, J. W., Kaiser, W. J. & Mocarski, E. S. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7, 302\u2013313 (2010).","journal-title":"Cell Host Microbe"},{"key":"1002_CR21","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.coviro.2013.05.019","volume":"3","author":"WJ Kaiser","year":"2013","unstructured":"Kaiser, W. J., Upton, J. W. & Mocarski, E. S. Viral modulation of programmed necrosis. Curr. Opin. Virol. 3, 296\u2013306 (2013).","journal-title":"Curr. Opin. Virol."},{"key":"1002_CR22","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01101-19","author":"S Balachandran","year":"2020","unstructured":"Balachandran, S. & Rall, G. F. Benefits and perils of necroptosis in influenza virus infection. J. Virol. https:\/\/doi.org\/10.1128\/JVI.01101-19 (2020).","journal-title":"J. Virol."},{"key":"1002_CR23","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41422-020-00393-6","volume":"30","author":"S Zhou","year":"2020","unstructured":"Zhou, S. et al. Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration. Cell Res. 30, 1063\u20131077 (2020).","journal-title":"Cell Res."},{"key":"1002_CR24","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41577-022-00792-3","volume":"23","author":"G van Loo","year":"2023","unstructured":"van Loo, G. & Bertrand, M. J. M. Death by TNF: a road to inflammation. Nat. Rev. Immunol. 23, 289\u2013303 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"1002_CR25","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0092-8674(03)00521-X","volume":"114","author":"O Micheau","year":"2003","unstructured":"Micheau, O. & Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114, 181\u2013190 (2003).","journal-title":"Cell"},{"key":"1002_CR26","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.molcel.2008.05.014","volume":"30","author":"MJ Bertrand","year":"2008","unstructured":"Bertrand, M. J. et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell 30, 689\u2013700 (2008).","journal-title":"Mol. Cell"},{"key":"1002_CR27","doi-asserted-by":"publisher","first-page":"11778","DOI":"10.1073\/pnas.0711122105","volume":"105","author":"DJ Mahoney","year":"2008","unstructured":"Mahoney, D. J. et al. Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation. Proc. Natl Acad. Sci. USA 105, 11778\u201311783 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR28","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1038\/emboj.2012.18","volume":"31","author":"M Moulin","year":"2012","unstructured":"Moulin, M. et al. IAPs limit activation of RIP kinases by TNF receptor 1 during development. EMBO J. 31, 1679\u20131691 (2012).","journal-title":"EMBO J."},{"key":"1002_CR29","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nature09816","volume":"471","author":"B Gerlach","year":"2011","unstructured":"Gerlach, B. et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471, 591\u2013596 (2011).","journal-title":"Nature"},{"key":"1002_CR30","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nature09815","volume":"471","author":"F Tokunaga","year":"2011","unstructured":"Tokunaga, F. et al. SHARPIN is a component of the NF-\u03baB-activating linear ubiquitin chain assembly complex. Nature 471, 633\u2013636 (2011).","journal-title":"Nature"},{"key":"1002_CR31","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nature09814","volume":"471","author":"F Ikeda","year":"2011","unstructured":"Ikeda, F. et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature 471, 637\u2013641 (2011).","journal-title":"Nature"},{"key":"1002_CR32","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.semcdb.2020.08.008","volume":"109","author":"DS Simpson","year":"2021","unstructured":"Simpson, D. S., Gabrielyan, A. & Feltham, R. RIPK1 ubiquitination: evidence, correlations and the undefined. Semin. Cell Dev. Biol. 109, 76\u201385 (2021).","journal-title":"Semin. Cell Dev. Biol."},{"key":"1002_CR33","doi-asserted-by":"publisher","first-page":"24295","DOI":"10.1074\/jbc.C800128200","volume":"283","author":"E Varfolomeev","year":"2008","unstructured":"Varfolomeev, E. et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J. Biol. Chem. 283, 24295\u201324299 (2008).","journal-title":"J. Biol. Chem."},{"key":"1002_CR34","first-page":"151","volume":"566","author":"SM Park","year":"2004","unstructured":"Park, S. M., Yoon, J. B. & Lee, T. H. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett. 566, 151\u2013156 (2004).","journal-title":"FEBS Lett."},{"key":"1002_CR35","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.molcel.2009.10.013","volume":"36","author":"TL Haas","year":"2009","unstructured":"Haas, T. L. et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol. Cell 36, 831\u2013844 (2009).","journal-title":"Mol. Cell"},{"key":"1002_CR36","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1016\/j.celrep.2015.11.009","volume":"13","author":"P Draber","year":"2015","unstructured":"Draber, P. et al. LUBAC-recruited CYLD and A20 regulate gene activation and cell death by exerting opposing effects on linear ubiquitin in signaling complexes. Cell Rep. 13, 2258\u20132272 (2015).","journal-title":"Cell Rep."},{"key":"1002_CR37","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/ncb1821","volume":"11","author":"F Tokunaga","year":"2009","unstructured":"Tokunaga, F. et al. Involvement of linear polyubiquitylation of NEMO in NF-\u03baB activation. Nat. Cell Biol. 11, 123\u2013132 (2009).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR38","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/35085597","volume":"412","author":"C Wang","year":"2001","unstructured":"Wang, C. et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346\u2013351 (2001).","journal-title":"Nature"},{"key":"1002_CR39","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.molcel.2006.03.026","volume":"22","author":"CK Ea","year":"2006","unstructured":"Ea, C. K., Deng, L., Xia, Z. P., Pineda, G. & Chen, Z. J. Activation of IKK by TNF\u03b1\u00a0requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol. Cell 22, 245\u2013257 (2006).","journal-title":"Mol. Cell"},{"key":"1002_CR40","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1101\/gad.9.13.1586","volume":"9","author":"Z Chen","year":"1995","unstructured":"Chen, Z. et al. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 9, 1586\u20131597 (1995).","journal-title":"Genes Dev."},{"key":"1002_CR41","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1084\/jem.189.11.1839","volume":"189","author":"ZW Li","year":"1999","unstructured":"Li, Z. W. et al. The IKK\u03b2\u00a0subunit of I\u03baB kinase (IKK) is essential for nuclear factor \u03baB activation and prevention of apoptosis. J. Exp. Med. 189, 1839\u20131845 (1999).","journal-title":"J. Exp. Med."},{"key":"1002_CR42","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1126\/science.284.5412.321","volume":"284","author":"Q Li","year":"1999","unstructured":"Li, Q., Van Antwerp, D., Mercurio, F., Lee, K. F. & Verma, I. M. Severe liver degeneration in mice lacking the I\u03baB kinase 2 gene. Science 284, 321\u2013325 (1999).","journal-title":"Science"},{"key":"1002_CR43","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1128\/MCB.21.16.5299-5305.2001","volume":"21","author":"O Micheau","year":"2001","unstructured":"Micheau, O., Lens, S., Gaide, O., Alevizopoulos, K. & Tschopp, J. NF-kappaB signals induce the expression of c-FLIP. Mol. Cell Biol. 21, 5299\u20135305 (2001).","journal-title":"Mol. Cell Biol."},{"key":"1002_CR44","doi-asserted-by":"publisher","first-page":"6034","DOI":"10.1128\/MCB.22.17.6034-6045.2002","volume":"22","author":"KL He","year":"2002","unstructured":"He, K. L. & Ting, A. T. A20 inhibits tumor necrosis factor (TNF) alpha-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNF receptor 1 complex in Jurkat T cells. Mol. Cell Biol. 22, 6034\u20136045 (2002).","journal-title":"Mol. Cell Biol."},{"key":"1002_CR45","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nature02794","volume":"430","author":"IE Wertz","year":"2004","unstructured":"Wertz, I. E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-\u03baB signalling. Nature 430, 694\u2013699 (2004).","journal-title":"Nature"},{"key":"1002_CR46","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.it.2023.05.007","volume":"44","author":"J Huyghe","year":"2023","unstructured":"Huyghe, J., Priem, D. & Bertrand, M. J. M. Cell death checkpoints in the TNF pathway. Trends Immunol. 44, 628\u2013643 (2023).","journal-title":"Trends Immunol."},{"key":"1002_CR47","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2008.03.036","volume":"133","author":"L Wang","year":"2008","unstructured":"Wang, L., Du, F. & Wang, X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133, 693\u2013703 (2008).","journal-title":"Cell"},{"key":"1002_CR48","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.jtbi.2007.10.030","volume":"250","author":"N Okazaki","year":"2008","unstructured":"Okazaki, N., Asano, R., Kinoshita, T. & Chuman, H. Simple computational models of type I\/type II cells in Fas signaling-induced apoptosis. J. Theor. Biol. 250, 621\u2013633 (2008).","journal-title":"J. Theor. Biol."},{"key":"1002_CR49","doi-asserted-by":"publisher","first-page":"30321","DOI":"10.3390\/ijms161226232","volume":"16","author":"Y Tsuchiya","year":"2015","unstructured":"Tsuchiya, Y., Nakabayashi, O. & Nakano, H. FLIP the switch: regulation of apoptosis and necroptosis by cFLIP. Int. J. Mol. Sci. 16, 30321\u201330341 (2015).","journal-title":"Int. J. Mol. Sci."},{"key":"1002_CR50","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1126\/science.add6967","volume":"378","author":"J Huyghe","year":"2022","unstructured":"Huyghe, J. et al. ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway. Science 378, 1201\u20131207 (2022).","journal-title":"Science"},{"key":"1002_CR51","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.tcb.2019.12.009","volume":"30","author":"T Delanghe","year":"2020","unstructured":"Delanghe, T., Dondelinger, Y. & Bertrand, M. J. M. RIPK1 kinase-dependent death: a symphony of phosphorylation events. Trends Cell Biol. 30, 189\u2013200 (2020).","journal-title":"Trends Cell Biol."},{"key":"1002_CR52","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.molcel.2015.07.032","volume":"60","author":"Y Dondelinger","year":"2015","unstructured":"Dondelinger, Y. et al. NF-\u03baB-independent role of IKK\u03b1\/IKK\u03b2 in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling. Mol. Cell 60, 63\u201376 (2015).","journal-title":"Mol. Cell"},{"key":"1002_CR53","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/j.cell.2018.07.041","volume":"174","author":"D Xu","year":"2018","unstructured":"Xu, D. et al. TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging. Cell 174, 1477\u20131491 e1419 (2018). Reference 53 uncovers a molecular bridge between ageing and neurodegeneration, demonstrating that the age-related decline of the inhibitor TAK1 collaborates with genetic TBK1 deficiencies to unleash toxic RIPK1 activation, driving ALS and FTD pathogenesis.","journal-title":"Cell"},{"key":"1002_CR54","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41556-018-0229-6","volume":"20","author":"E Lafont","year":"2018","unstructured":"Lafont, E. et al. TBK1 and IKK\u03b5 prevent TNF-induced cell death by RIPK1 phosphorylation. Nat. Cell Biol. 20, 1389\u20131399 (2018).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00406-w","volume":"8","author":"J Geng","year":"2017","unstructured":"Geng, J. et al. Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat. Commun. 8, 359 (2017).","journal-title":"Nat. Commun."},{"key":"1002_CR56","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/ncb3614","volume":"19","author":"MB Menon","year":"2017","unstructured":"Menon, M. B. et al. p38(MAPK)\/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat. Cell Biol. 19, 1248\u20131259 (2017).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR57","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.molcel.2017.05.003","volume":"66","author":"I Jaco","year":"2017","unstructured":"Jaco, I. et al. MK2 phosphorylates RIPK1 to prevent TNF-induced cell death. Mol. Cell 66, 698\u2013710 e695 (2017).","journal-title":"Mol. Cell"},{"key":"1002_CR58","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/ncb3608","volume":"19","author":"Y Dondelinger","year":"2017","unstructured":"Dondelinger, Y. et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat. Cell Biol. 19, 1237\u20131247 (2017).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR59","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.celrep.2014.08.066","volume":"9","author":"N Peltzer","year":"2014","unstructured":"Peltzer, N. et al. HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Rep. 9, 153\u2013165 (2014).","journal-title":"Cell Rep."},{"key":"1002_CR60","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41586-018-0064-8","volume":"557","author":"N Peltzer","year":"2018","unstructured":"Peltzer, N. et al. LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis. Nature 557, 112\u2013117 (2018).","journal-title":"Nature"},{"key":"1002_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12033-8","volume":"10","author":"Y Tang","year":"2019","unstructured":"Tang, Y. et al. K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell death during embryogenesis and inflammation. Nat. Commun. 10, 4157 (2019).","journal-title":"Nat. Commun."},{"key":"1002_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11839-w","volume":"10","author":"X Zhang","year":"2019","unstructured":"Zhang, X. et al. Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis. Nat. Commun. 10, 4158 (2019).","journal-title":"Nat. Commun."},{"key":"1002_CR63","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41586-019-1830-y","volume":"577","author":"P Tao","year":"2020","unstructured":"Tao, P. et al. A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1. Nature 577, 109\u2013114 (2020).","journal-title":"Nature"},{"key":"1002_CR64","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/s41586-019-1548-x","volume":"574","author":"K Newton","year":"2019","unstructured":"Newton, K. et al. Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature 574, 428\u2013431 (2019).","journal-title":"Nature"},{"key":"1002_CR65","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41586-019-1828-5","volume":"577","author":"N Lalaoui","year":"2020","unstructured":"Lalaoui, N. et al. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease. Nature 577, 103\u2013108 (2020). References 63, 64 and 65 provided evidence that caspase-8 restricts RIPK1-dependent cell death and inflammation through cleavage of RIPK1.","journal-title":"Nature"},{"key":"1002_CR66","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nature10400","volume":"477","author":"C Gunther","year":"2011","unstructured":"Gunther, C. et al. Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature 477, 335\u2013339 (2011).","journal-title":"Nature"},{"key":"1002_CR67","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41586-019-1752-8","volume":"575","author":"K Newton","year":"2019","unstructured":"Newton, K. et al. Activity of caspase-8 determines plasticity between cell death pathways. Nature 575, 679\u2013682 (2019).","journal-title":"Nature"},{"key":"1002_CR68","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s41586-019-1770-6","volume":"575","author":"M Fritsch","year":"2019","unstructured":"Fritsch, M. et al. Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature 575, 683\u2013687 (2019).","journal-title":"Nature"},{"key":"1002_CR69","doi-asserted-by":"publisher","first-page":"E2786","DOI":"10.1073\/pnas.1616829114","volume":"114","author":"LP Daley-Bauer","year":"2017","unstructured":"Daley-Bauer, L. P. et al. Mouse cytomegalovirus M36 and M45 death suppressors cooperate to prevent inflammation resulting from antiviral programmed cell death pathways. Proc. Natl Acad. Sci. USA 114, E2786\u2013e2795 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR70","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020104469","volume":"39","author":"H Ashida","year":"2020","unstructured":"Ashida, H., Sasakawa, C. & Suzuki, T. A unique bacterial tactic to circumvent the cell death crosstalk induced by blockade of caspase-8. EMBO J. 39, e104469 (2020).","journal-title":"EMBO J."},{"key":"1002_CR71","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.molcel.2020.09.004","volume":"80","author":"ZH Yang","year":"2020","unstructured":"Yang, Z. H. et al. A non-canonical PDK1-RSK signal diminishes pro-caspase-8-mediated necroptosis blockade. Mol. Cell 80, 296\u2013310.e296 (2020).","journal-title":"Mol. Cell"},{"key":"1002_CR72","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1016\/j.cell.2018.03.032","volume":"173","author":"M Mompean","year":"2018","unstructured":"Mompean, M. et al. The structure of the necrosome RIPK1-RIPK3 core, a human hetero-amyloid signaling complex. Cell 173, 1244\u20131253.e1210 (2018).","journal-title":"Cell"},{"key":"1002_CR73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110476118","author":"W Liang","year":"2021","unstructured":"Liang, W. et al. Necroptosis activates UPR sensors without disrupting their binding with GRP78. Proc. Natl Acad. Sci. USA https:\/\/doi.org\/10.1073\/pnas.2110476118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR74","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1512968","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang, Y. et al. MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics. Front. Pharmacol. 16, 1512968 (2025).","journal-title":"Front. Pharmacol."},{"key":"1002_CR75","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16887-1","volume":"11","author":"AL Samson","year":"2020","unstructured":"Samson, A. L. et al. MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis. Nat. Commun. 11, 3151 (2020).","journal-title":"Nat. Commun."},{"key":"1002_CR76","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41586-025-09741-1","volume":"649","author":"H Noh","year":"2026","unstructured":"Noh, H., Hashem, Z., Boms, E. & Najafov, A. SIGLEC12 mediates plasma membrane rupture during necroptotic cell death. Nature 649, 460\u2013466 (2026).","journal-title":"Nature"},{"key":"1002_CR77","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22400-z","volume":"12","author":"SE Garnish","year":"2021","unstructured":"Garnish, S. E. et al. Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis. Nat. Commun. 12, 2211 (2021).","journal-title":"Nat. Commun."},{"key":"1002_CR78","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1016\/j.molcel.2025.06.005","volume":"85","author":"Z Ding","year":"2025","unstructured":"Ding, Z., Wang, R., Li, Y. & Wang, X. MLKL activates the cGAS-STING pathway by releasing mitochondrial DNA upon necroptosis induction. Mol. Cell 85, 2610\u20132625.e2615 (2025).","journal-title":"Mol. Cell"},{"key":"1002_CR79","doi-asserted-by":"publisher","first-page":"e2507028122","DOI":"10.1073\/pnas.2507028122","volume":"122","author":"Y Ma","year":"2025","unstructured":"Ma, Y. et al. Intercellular propagation of RIPK1\/RIPK3 amyloid fibrils. Proc. Natl Acad. Sci. USA 122, e2507028122 (2025).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR80","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41556-024-01374-2","volume":"26","author":"Y Yang","year":"2024","unstructured":"Yang, Y. et al. Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1. Nat. Cell Biol. 26, 567\u2013580 (2024). Reference 80 provided evidence that RIPK1 drives nuclear necroptosis on prelamin A accumulation.","journal-title":"Nat. Cell Biol."},{"key":"1002_CR81","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1126\/science.abn1725","volume":"380","author":"T Zhang","year":"2023","unstructured":"Zhang, T. et al. Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. Science 380, 1372\u20131380 (2023).","journal-title":"Science"},{"key":"1002_CR82","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/nri3713","volume":"14","author":"NJ Gay","year":"2014","unstructured":"Gay, N. J., Symmons, M. F., Gangloff, M. & Bryant, C. E. Assembly and localization of Toll-like receptor signalling complexes. Nat. Rev. Immunol. 14, 546\u2013558 (2014).","journal-title":"Nat. Rev. Immunol."},{"key":"1002_CR83","doi-asserted-by":"publisher","first-page":"31268","DOI":"10.1074\/jbc.M113.462341","volume":"288","author":"WJ Kaiser","year":"2013","unstructured":"Kaiser, W. J. et al. Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J. Biol. Chem. 288, 31268\u201331279 (2013).","journal-title":"J. Biol. Chem."},{"key":"1002_CR84","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.immuni.2016.06.007","volume":"45","author":"M Najjar","year":"2016","unstructured":"Najjar, M. et al. RIPK1 and RIPK3 kinases promote cell-death-independent inflammation by toll-like receptor 4. Immunity 45, 46\u201359 (2016).","journal-title":"Immunity"},{"key":"1002_CR85","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.immuni.2019.01.007","volume":"50","author":"X Li","year":"2019","unstructured":"Li, X. et al. O-GlcNAc transferase suppresses inflammation and necroptosis by targeting receptor-interacting serine\/threonine-protein kinase 3. Immunity 50, 576\u2013590.e576 (2019).","journal-title":"Immunity"},{"key":"1002_CR86","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/ni.2397","volume":"13","author":"N Robinson","year":"2012","unstructured":"Robinson, N. et al. Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium. Nat. Immunol. 13, 954\u2013962 (2012).","journal-title":"Nat. Immunol."},{"key":"1002_CR87","doi-asserted-by":"publisher","first-page":"E3109","DOI":"10.1073\/pnas.1301218110","volume":"110","author":"RJ Thapa","year":"2013","unstructured":"Thapa, R. J. et al. Interferon-induced RIP1\/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc. Natl Acad. Sci. USA 110, E3109\u2013E3118 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR88","doi-asserted-by":"publisher","first-page":"e2426660122","DOI":"10.1073\/pnas.2426660122","volume":"122","author":"X Huang","year":"2025","unstructured":"Huang, X. et al. PARP12-mediated mono-ADP-ribosylation as a checkpoint for necroptosis and apoptosis. Proc. Natl Acad. Sci. USA 122, e2426660122 (2025).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR89","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/s41423-019-0237-x","volume":"17","author":"D Yang","year":"2020","unstructured":"Yang, D. et al. ZBP1 mediates interferon-induced necroptosis. Cell Mol. Immunol. 17, 356\u2013368 (2020).","journal-title":"Cell Mol. Immunol."},{"key":"1002_CR90","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0378-1119(99)00419-9","volume":"240","author":"Y Fu","year":"1999","unstructured":"Fu, Y. et al. Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display. Gene 240, 157\u2013163 (1999).","journal-title":"Gene"},{"key":"1002_CR91","doi-asserted-by":"publisher","first-page":"20671","DOI":"10.1073\/pnas.0810463106","volume":"105","author":"SC Ha","year":"2008","unstructured":"Ha, S. C. et al. The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA. Proc. Natl Acad. Sci. USA 105, 20671\u201320676 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR92","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/0022-2836(72)90457-3","volume":"67","author":"FM Pohl","year":"1972","unstructured":"Pohl, F. M. & Jovin, T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J. Mol. Biol. 67, 375\u2013396 (1972).","journal-title":"J. Mol. Biol."},{"key":"1002_CR93","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1021\/bi00296a009","volume":"23","author":"A Moller","year":"1984","unstructured":"Moller, A., Nordheim, A., Kozlowski, S. A., Patel, D. J. & Rich, A. Bromination stabilizes poly(dG-dC) in the Z-DNA form under low-salt conditions. Biochemistry 23, 54\u201362 (1984).","journal-title":"Biochemistry"},{"key":"1002_CR94","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1126\/science.2678475","volume":"246","author":"AR Rahmouni","year":"1989","unstructured":"Rahmouni, A. R. & Wells, R. D. Stabilization of Z DNA in vivo by localized supercoiling. Science 246, 358\u2013363 (1989).","journal-title":"Science"},{"key":"1002_CR95","doi-asserted-by":"publisher","first-page":"e3002845","DOI":"10.1371\/journal.pbio.3002845","volume":"23","author":"OT Amusan","year":"2025","unstructured":"Amusan, O. T. et al. RIPK1 is required for ZBP1-driven necroptosis in human cells. PLoS Biol. 23, e3002845 (2025).","journal-title":"PLoS Biol."},{"key":"1002_CR96","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.chom.2016.09.014","volume":"20","author":"RJ Thapa","year":"2016","unstructured":"Thapa, R. J. et al. DAI senses influenza a virus genomic RNA and activates RIPK3-dependent cell death. Cell Host Microbe 20, 674\u2013681 (2016).","journal-title":"Cell Host Microbe"},{"key":"1002_CR97","doi-asserted-by":"publisher","DOI":"10.1172\/JCI180451","author":"R Liu","year":"2024","unstructured":"Liu, R. et al. ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia\/reperfusion injury. J. Clin. Invest. https:\/\/doi.org\/10.1172\/JCI180451 (2024).","journal-title":"J. Clin. Invest."},{"key":"1002_CR98","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/s41586-020-2129-8","volume":"580","author":"H Jiao","year":"2020","unstructured":"Jiao, H. et al. Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. Nature 580, 391\u2013395 (2020).","journal-title":"Nature"},{"key":"1002_CR99","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.immuni.2020.04.002","volume":"52","author":"R Schwarzer","year":"2020","unstructured":"Schwarzer, R., Jiao, H., Wachsmuth, L., Tresch, A. & Pasparakis, M. FADD and caspase-8 regulate gut homeostasis and inflammation by controlling MLKL- and GSDMD-mediated death of intestinal epithelial cells. Immunity 52, 978\u2013993.e976 (2020).","journal-title":"Immunity"},{"key":"1002_CR100","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.15252\/embj.201796476","volume":"36","author":"J Maelfait","year":"2017","unstructured":"Maelfait, J. et al. Sensing of viral and endogenous RNA by ZBP1\/DAI induces necroptosis. EMBO J. 36, 2529\u20132543 (2017).","journal-title":"EMBO J."},{"key":"1002_CR101","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1126\/science.abg5251","volume":"376","author":"F Yuan","year":"2022","unstructured":"Yuan, F. et al. Z-DNA binding protein 1 promotes heatstroke-induced cell death. Science 376, 609\u2013615 (2022).","journal-title":"Science"},{"key":"1002_CR102","doi-asserted-by":"publisher","first-page":"11506","DOI":"10.1073\/pnas.1700999114","volume":"114","author":"H Koehler","year":"2017","unstructured":"Koehler, H. et al. Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3. Proc. Natl Acad. Sci. USA 114, 11506\u201311511 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR103","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1016\/j.chom.2021.05.009","volume":"29","author":"H Koehler","year":"2021","unstructured":"Koehler, H. et al. Vaccinia virus E3 prevents sensing of Z-RNA to block ZBP1-dependent necroptosis. Cell Host Microbe 29, 1266\u20131276.e1265 (2021).","journal-title":"Cell Host Microbe"},{"key":"1002_CR104","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41422-022-00775-y","volume":"33","author":"S Li","year":"2023","unstructured":"Li, S. et al. SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses. Cell Res. 33, 201\u2013214 (2023).","journal-title":"Cell Res."},{"key":"1002_CR105","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.cell.2020.02.050","volume":"180","author":"T Zhang","year":"2020","unstructured":"Zhang, T. et al. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis. Cell 180, 1115\u20131129.e1113 (2020).","journal-title":"Cell"},{"key":"1002_CR106","doi-asserted-by":"publisher","unstructured":"Nemegeer, J. et al. Z\u03b1 domain-dependent ZBP1 condensate formation induces an amyloidal necroptotic signalling complex. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.06.06.658343 (2025).","DOI":"10.1101\/2025.06.06.658343"},{"key":"1002_CR107","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09705-5","author":"C Yin","year":"2025","unstructured":"Yin, C. et al. Host cell Z-RNAs activate ZBP1 during virus infections. Nature https:\/\/doi.org\/10.1038\/s41586-025-09705-5 (2025).","journal-title":"Nature"},{"key":"1002_CR108","doi-asserted-by":"publisher","first-page":"eabo6294","DOI":"10.1126\/sciimmunol.abo6294","volume":"7","author":"R Karki","year":"2022","unstructured":"Karki, R. et al. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Sci. Immunol. 7, eabo6294 (2022).","journal-title":"Sci. Immunol."},{"key":"1002_CR109","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/nature20558","volume":"540","author":"J Lin","year":"2016","unstructured":"Lin, J. et al. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 540, 124\u2013128 (2016).","journal-title":"Nature"},{"key":"1002_CR110","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.4049\/jimmunol.1900216","volume":"203","author":"JP Ingram","year":"2019","unstructured":"Ingram, J. P. et al. ZBP1\/DAI drives RIPK3-mediated cell death induced by IFNs in the absence of RIPK1. J. Immunol. 203, 1348\u20131355 (2019).","journal-title":"J. Immunol."},{"key":"1002_CR111","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1016\/j.immuni.2024.04.016","volume":"57","author":"T Imai","year":"2024","unstructured":"Imai, T. et al. The RIPK1 death domain restrains ZBP1- and TRIF-mediated cell death and inflammation. Immunity 57, 1497\u20131513.e1496 (2024).","journal-title":"Immunity"},{"key":"1002_CR112","doi-asserted-by":"publisher","first-page":"114335","DOI":"10.1016\/j.celrep.2024.114335","volume":"43","author":"DA Rodriguez","year":"2024","unstructured":"Rodriguez, D. A. et al. The interaction between RIPK1 and FADD controls perinatal lethality and inflammation. Cell Rep. 43, 114335 (2024).","journal-title":"Cell Rep."},{"key":"1002_CR113","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41418-024-01286-6","volume":"31","author":"M Solon","year":"2024","unstructured":"Solon, M. et al. ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1. Cell Death Differ. 31, 672\u2013682 (2024).","journal-title":"Cell Death Differ."},{"key":"1002_CR114","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/nature20559","volume":"540","author":"K Newton","year":"2016","unstructured":"Newton, K. et al. RIPK1 inhibits ZBP1-driven necroptosis during development. Nature 540, 129\u2013133 (2016). Reference 114 discovers that the RHIM domain of RIPK1 acts as a critical developmental brake that prevents the viral sensor ZBP1 from aberrantly binding to RIPK3 and triggering lethal necroptosis.","journal-title":"Nature"},{"key":"1002_CR115","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nature13608","volume":"513","author":"M Dannappel","year":"2014","unstructured":"Dannappel, M. et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513, 90\u201394 (2014).","journal-title":"Nature"},{"key":"1002_CR116","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S1074-7613(00)80535-X","volume":"8","author":"MA Kelliher","year":"1998","unstructured":"Kelliher, M. A. et al. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 8, 297\u2013303 (1998).","journal-title":"Immunity"},{"key":"1002_CR117","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1126\/science.aar2641","volume":"361","author":"D Cuchet-Lourenco","year":"2018","unstructured":"Cuchet-Lourenco, D. et al. Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science 361, 810\u2013813 (2018).","journal-title":"Science"},{"key":"1002_CR118","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1073\/pnas.1813582116","volume":"116","author":"Y Li","year":"2019","unstructured":"Li, Y. et al. Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc. Natl Acad. Sci. USA 116, 970\u2013975 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR119","doi-asserted-by":"publisher","first-page":"e2207240119","DOI":"10.1073\/pnas.2207240119","volume":"119","author":"DA Rodriguez","year":"2022","unstructured":"Rodriguez, D. A. et al. Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis. Proc. Natl Acad. Sci. USA 119, e2207240119 (2022).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR120","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09536-4","author":"K Kelepouras","year":"2025","unstructured":"Kelepouras, K. et al. STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD. Nature https:\/\/doi.org\/10.1038\/s41586-025-09536-4 (2025).","journal-title":"Nature"},{"key":"1002_CR121","doi-asserted-by":"publisher","first-page":"114221","DOI":"10.1016\/j.celrep.2024.114221","volume":"43","author":"ZY Cai","year":"2024","unstructured":"Cai, Z. Y. et al. A ZBP1 isoform blocks ZBP1-mediated cell death. Cell Rep. 43, 114221 (2024).","journal-title":"Cell Rep."},{"key":"1002_CR122","doi-asserted-by":"publisher","first-page":"5037","DOI":"10.1038\/s44318-024-00238-7","volume":"43","author":"M Nagata","year":"2024","unstructured":"Nagata, M., Carvalho Schafer, Y., Wachsmuth, L. & Pasparakis, M. A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses. EMBO J. 43, 5037\u20135056 (2024).","journal-title":"EMBO J."},{"key":"1002_CR123","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/s41586-020-2127-x","volume":"580","author":"R Wang","year":"2020","unstructured":"Wang, R. et al. Gut stem cell necroptosis by genome instability triggers bowel inflammation. Nature 580, 386\u2013390 (2020). References 98 and 123 provided evidence that endogenous Z-RNA drives ZBP1-dependent cell death and inflammation.","journal-title":"Nature"},{"key":"1002_CR124","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1038\/s41586-022-04974-w","volume":"607","author":"R de Reuver","year":"2022","unstructured":"de Reuver, R. et al. ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation. Nature 607, 784\u2013789 (2022).","journal-title":"Nature"},{"key":"1002_CR125","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41586-022-04896-7","volume":"607","author":"NW Hubbard","year":"2022","unstructured":"Hubbard, N. W. et al. ADAR1 mutation causes ZBP1-dependent immunopathology. Nature 607, 769\u2013775 (2022).","journal-title":"Nature"},{"key":"1002_CR126","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/s41586-022-04878-9","volume":"607","author":"H Jiao","year":"2022","unstructured":"Jiao, H. et al. ADAR1 averts fatal type I interferon induction by ZBP1. Nature 607, 776\u2013783 (2022).","journal-title":"Nature"},{"key":"1002_CR127","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41586-022-04753-7","volume":"606","author":"T Zhang","year":"2022","unstructured":"Zhang, T. et al. ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis. Nature 606, 594\u2013602 (2022).","journal-title":"Nature"},{"key":"1002_CR128","doi-asserted-by":"publisher","first-page":"eabq0837","DOI":"10.1126\/scisignal.abq0837","volume":"16","author":"M Szczerba","year":"2023","unstructured":"Szczerba, M. et al. Canonical cellular stress granules are required for arsenite-induced necroptosis mediated by Z-DNA-binding protein 1. Sci. Signal. 16, eabq0837 (2023).","journal-title":"Sci. Signal."},{"key":"1002_CR129","doi-asserted-by":"publisher","first-page":"113377","DOI":"10.1016\/j.celrep.2023.113377","volume":"42","author":"T Yang","year":"2023","unstructured":"Yang, T. et al. Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis. Cell Rep. 42, 113377 (2023).","journal-title":"Cell Rep."},{"key":"1002_CR130","doi-asserted-by":"publisher","first-page":"e2514837122","DOI":"10.1073\/pnas.2514837122","volume":"122","author":"H Lei","year":"2025","unstructured":"Lei, H. et al. Stress granule-mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging. Proc. Natl Acad. Sci. USA 122, e2514837122 (2025).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR131","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1016\/j.molcel.2025.03.023","volume":"85","author":"ZH Yang","year":"2025","unstructured":"Yang, Z. H. et al. ZBP1 senses splicing aberration through Z-RNA to promote cell death. Mol. Cell 85, 1775\u20131789.e1775 (2025).","journal-title":"Mol. Cell"},{"key":"1002_CR132","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1016\/j.molcel.2025.04.004","volume":"85","author":"J He","year":"2025","unstructured":"He, J. et al. ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. Mol. Cell 85, 1790\u20131805.e1797 (2025).","journal-title":"Mol. Cell"},{"key":"1002_CR133","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/s41586-023-05710-8","volume":"614","author":"J Nassour","year":"2023","unstructured":"Nassour, J. et al. Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis. Nature 614, 767\u2013773 (2023).","journal-title":"Nature"},{"key":"1002_CR134","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1016\/j.immuni.2025.09.019","volume":"58","author":"D Priem","year":"2025","unstructured":"Priem, D. et al. ATG9A-mediated autophagy prevents inflammatory skin disease by limiting TNFR1-driven STING activation and ZBP1-dependent cell death. Immunity 58, 2972\u20132988.e2976 (2025).","journal-title":"Immunity"},{"key":"1002_CR135","doi-asserted-by":"publisher","first-page":"3013","DOI":"10.1016\/j.cell.2023.05.039","volume":"186","author":"Y Lei","year":"2023","unstructured":"Lei, Y. et al. Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity. Cell 186, 3013\u20133032.e3022 (2023).","journal-title":"Cell"},{"key":"1002_CR136","doi-asserted-by":"publisher","first-page":"eado1710","DOI":"10.1126\/sciimmunol.ado1710","volume":"10","author":"B Klein","year":"2025","unstructured":"Klein, B. et al. Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity. Sci. Immunol. 10, eado1710 (2025).","journal-title":"Sci. Immunol."},{"key":"1002_CR137","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1039\/C8OB00030A","volume":"16","author":"V Vongsutilers","year":"2018","unstructured":"Vongsutilers, V. & Gannett, P. M. C8-guanine modifications: effect on Z-DNA formation and its role in cancer. Org. Biomol. Chem. 16, 2198\u20132209 (2018).","journal-title":"Org. Biomol. Chem."},{"key":"1002_CR138","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.07.024","author":"Z Song","year":"2025","unstructured":"Song, Z. et al. Innate immune sensing of Z-nucleic acids by ZBP1-RIPK1 axis drives neuroinflammation in Alzheimer\u2019s disease. Immunity https:\/\/doi.org\/10.1016\/j.immuni.2025.07.024 (2025). Reference 138 provided evidence that oxidative stress induces 8-oxo-dG modification in mitochondrial DNA, thereby promoting Z-DNA formation in pathophysiological conditions.","journal-title":"Immunity"},{"key":"1002_CR139","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41586-023-06889-6","volume":"625","author":"MG Cho","year":"2024","unstructured":"Cho, M. G. et al. MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis. Nature 625, 585\u2013592 (2024).","journal-title":"Nature"},{"key":"1002_CR140","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/s41418-020-00629-3","volume":"28","author":"M Kist","year":"2021","unstructured":"Kist, M. et al. Impaired RIPK1 ubiquitination sensitizes mice to TNF toxicity and inflammatory cell death. Cell Death Differ. 28, 985\u20131000 (2021).","journal-title":"Cell Death Differ."},{"key":"1002_CR141","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19935-y","volume":"11","author":"X Li","year":"2020","unstructured":"Li, X. et al. Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners. Nat. Commun. 11, 6364 (2020).","journal-title":"Nat. Commun."},{"key":"1002_CR142","doi-asserted-by":"publisher","first-page":"11944","DOI":"10.1073\/pnas.1715742114","volume":"114","author":"H Wang","year":"2017","unstructured":"Wang, H. et al. PELI1 functions as a dual modulator of necroptosis and apoptosis by regulating ubiquitination of RIPK1 and mRNA levels of c-FLIP. Proc. Natl Acad. Sci. USA 114, 11944\u201311949 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR143","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.molcel.2018.05.016","volume":"70","author":"SW Choi","year":"2018","unstructured":"Choi, S. W. et al. PELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent proteasomal degradation. Mol. Cell 70, 920\u2013935 e927 (2018).","journal-title":"Mol. Cell"},{"key":"1002_CR144","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ncb3314","volume":"18","author":"J Seo","year":"2016","unstructured":"Seo, J. et al. CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. Nat. Cell Biol. 18, 291\u2013302 (2016).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR145","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20250279","author":"L Koerner","year":"2025","unstructured":"Koerner, L., Li, X., Silnov, E., Laurien, L. & Pasparakis, M. RIPK1 autophosphorylation at S161 mediates cell death and inflammation. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20250279 (2025).","journal-title":"J. Exp. Med."},{"key":"1002_CR146","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20250277","author":"T Han","year":"2025","unstructured":"Han, T. et al. RIPK1 S161 phosphorylation promotes further autophosphorylation and cecal necroptosis in TNF-treated mice. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20250277 (2025).","journal-title":"J. Exp. Med."},{"key":"1002_CR147","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15466-8","volume":"11","author":"L Laurien","year":"2020","unstructured":"Laurien, L. et al. Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation. Nat. Commun. 11, 1747 (2020).","journal-title":"Nat. Commun."},{"key":"1002_CR148","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09690-0","volume":"10","author":"Y Dondelinger","year":"2019","unstructured":"Dondelinger, Y. et al. Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation. Nat. Commun. 10, 1729 (2019).","journal-title":"Nat. Commun."},{"key":"1002_CR149","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1038\/s41564-024-01734-6","volume":"9","author":"Y Yang","year":"2024","unstructured":"Yang, Y. et al. Yersinia infection induces glucose depletion and AMPK-dependent inhibition of pyroptosis in mice. Nat. Microbiol. 9, 2144\u20132159 (2024).","journal-title":"Nat. Microbiol."},{"key":"1002_CR150","doi-asserted-by":"publisher","first-page":"4447","DOI":"10.1016\/j.cell.2021.07.026","volume":"184","author":"J Taft","year":"2021","unstructured":"Taft, J. et al. Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death. Cell 184, 4447\u20134463.e4420 (2021).","journal-title":"Cell"},{"key":"1002_CR151","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34080-4","volume":"13","author":"H Tu","year":"2022","unstructured":"Tu, H., Xiong, W., Zhang, J., Zhao, X. & Lin, X. Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation. Nat. Commun. 13, 6603 (2022).","journal-title":"Nat. Commun."},{"key":"1002_CR152","doi-asserted-by":"publisher","first-page":"E2001","DOI":"10.1073\/pnas.1722013115","volume":"115","author":"H Meng","year":"2018","unstructured":"Meng, H. et al. Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis. Proc. Natl Acad. Sci. USA 115, E2001\u2013E2009 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR153","doi-asserted-by":"publisher","first-page":"4419","DOI":"10.1016\/j.molcel.2024.10.002","volume":"84","author":"N Zhang","year":"2024","unstructured":"Zhang, N. et al. Palmitoylation licenses RIPK1 kinase activity and cytotoxicity in the TNF pathway. Mol. Cell 84, 4419\u20134435.e4410 (2024).","journal-title":"Mol. Cell"},{"key":"1002_CR154","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.molcel.2023.12.041","volume":"84","author":"S Hou","year":"2024","unstructured":"Hou, S. et al. PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis. Mol. Cell 84, 938\u2013954.e938 (2024).","journal-title":"Mol. Cell"},{"key":"1002_CR155","doi-asserted-by":"publisher","first-page":"eabh2332","DOI":"10.1126\/sciadv.abh2332","volume":"8","author":"L Liu","year":"2022","unstructured":"Liu, L. et al. Tankyrase-mediated ADP-ribosylation is a regulator of TNF-induced death. Sci. Adv. 8, eabh2332 (2022).","journal-title":"Sci. Adv."},{"key":"1002_CR156","doi-asserted-by":"publisher","first-page":"1160490","DOI":"10.3389\/fimmu.2023.1160490","volume":"14","author":"J Seo","year":"2023","unstructured":"Seo, J. et al. O-GlcNAcylation of RIPK1 rescues red blood cells from necroptosis. Front. Immunol. 14, 1160490 (2023).","journal-title":"Front. Immunol."},{"key":"1002_CR157","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34993-0","volume":"13","author":"L Yan","year":"2022","unstructured":"Yan, L. et al. SENP1 prevents steatohepatitis by suppressing RIPK1-driven apoptosis and inflammation. Nat. Commun. 13, 7153 (2022).","journal-title":"Nat. Commun."},{"key":"1002_CR158","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1016\/j.cmet.2025.05.014","volume":"37","author":"Z Chen","year":"2025","unstructured":"Chen, Z. et al. RIPK1 senses S-adenosylmethionine scarcity to drive cell death and inflammation. Cell Metab. 37, 1732\u20131749.e1739 (2025).","journal-title":"Cell Metab."},{"key":"1002_CR159","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20250603","author":"R Liu","year":"2026","unstructured":"Liu, R. et al. Adenosine metabolic clearance maintains liver homeostasis by licensing arginine methylation of RIPK1. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20250603 (2026).","journal-title":"J. Exp. Med."},{"key":"1002_CR160","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1038\/s41556-024-01540-6","volume":"26","author":"T Zhang","year":"2024","unstructured":"Zhang, T. et al. Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression. Nat. Cell Biol. 26, 2099\u20132114 (2024).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR161","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/s41556-023-01170-4","volume":"25","author":"T Zhang","year":"2023","unstructured":"Zhang, T. et al. Prolonged hypoxia alleviates prolyl hydroxylation-mediated suppression of RIPK1 to promote necroptosis and inflammation. Nat. Cell Biol. 25, 950\u2013962 (2023).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR162","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1101\/gad.13.19.2514","volume":"13","author":"Y Lin","year":"1999","unstructured":"Lin, Y., Devin, A., Rodriguez, Y. & Liu, Z. G. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 13, 2514\u20132526 (1999).","journal-title":"Genes Dev."},{"key":"1002_CR163","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61564","author":"D Li","year":"2020","unstructured":"Li, D. et al. Casein kinase 1G2 suppresses necroptosis-promoted testis aging by inhibiting receptor-interacting kinase 3. eLife https:\/\/doi.org\/10.7554\/eLife.61564 (2020).","journal-title":"eLife"},{"key":"1002_CR164","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2146-4","volume":"10","author":"SY Lee","year":"2019","unstructured":"Lee, S. Y. et al. Casein kinase-1\u03b31 and 3 stimulate tumor necrosis factor-induced necroptosis through RIPK3. Cell Death Dis. 10, 923 (2019).","journal-title":"Cell Death Dis."},{"key":"1002_CR165","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1073\/pnas.1917112117","volume":"117","author":"S Hanna-Addams","year":"2020","unstructured":"Hanna-Addams, S., Liu, S., Liu, H., Chen, S. & Wang, Z. CK1\u03b1, CK1\u03b4, and CK1\u03b5 are necrosome components which phosphorylate serine 227 of human RIPK3 to activate necroptosis. Proc. Natl Acad. Sci. USA 117, 1962\u20131970 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR166","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/ncb3120","volume":"17","author":"W Chen","year":"2015","unstructured":"Chen, W. et al. Ppm1b negatively regulates necroptosis through dephosphorylating Rip3. Nat. Cell Biol. 17, 434\u2013444 (2015).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR167","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/ni.3172","volume":"16","author":"M Onizawa","year":"2015","unstructured":"Onizawa, M. et al. The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Nat. Immunol. 16, 618\u2013627 (2015).","journal-title":"Nat. Immunol."},{"key":"1002_CR168","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/s41556-019-0356-8","volume":"21","author":"SB Lee","year":"2019","unstructured":"Lee, S. B. et al. The AMPK-Parkin axis negatively regulates necroptosis and tumorigenesis by inhibiting the necrosome. Nat. Cell Biol. 21, 940\u2013951 (2019).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR169","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1016\/j.cellsig.2007.05.016","volume":"19","author":"S Feng","year":"2007","unstructured":"Feng, S. et al. Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain. Cell. Signal. 19, 2056\u20132067 (2007).","journal-title":"Cell. Signal."},{"key":"1002_CR170","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41418-023-01255-5","volume":"31","author":"K Newton","year":"2024","unstructured":"Newton, K. et al. Caspase cleavage of RIPK3 after Asp(333) is dispensable for mouse embryogenesis. Cell Death Differ. 31, 254\u2013262 (2024).","journal-title":"Cell Death Differ."},{"key":"1002_CR171","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/s41418-024-01281-x","volume":"31","author":"HT Tran","year":"2024","unstructured":"Tran, H. T. et al. RIPK3 cleavage is dispensable for necroptosis inhibition but restricts NLRP3 inflammasome activation. Cell Death Differ. 31, 662\u2013671 (2024).","journal-title":"Cell Death Differ."},{"key":"1002_CR172","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1042\/BJ20131270","volume":"457","author":"JM Murphy","year":"2014","unstructured":"Murphy, J. M. et al. Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL. Biochem. J. 457, 369\u2013377 (2014).","journal-title":"Biochem. J."},{"key":"1002_CR173","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16823-3","volume":"11","author":"KA Davies","year":"2020","unstructured":"Davies, K. A. et al. Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues. Nat. Commun. 11, 3060 (2020).","journal-title":"Nat. Commun."},{"key":"1002_CR174","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.molcel.2019.05.022","volume":"75","author":"A Najafov","year":"2019","unstructured":"Najafov, A. et al. TAM kinases promote necroptosis by regulating oligomerization of MLKL. Mol. Cell 75, 457\u2013468.e454 (2019).","journal-title":"Mol. Cell"},{"key":"1002_CR175","doi-asserted-by":"publisher","first-page":"E7450","DOI":"10.1073\/pnas.1707531114","volume":"114","author":"S Liu","year":"2017","unstructured":"Liu, S. et al. MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis. Proc. Natl Acad. Sci. USA 114, E7450\u2013E7459 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR176","doi-asserted-by":"publisher","first-page":"17514","DOI":"10.1074\/jbc.M117.799353","volume":"292","author":"E Reynoso","year":"2017","unstructured":"Reynoso, E. et al. Thioredoxin-1 actively maintains the pseudokinase MLKL in a reduced state to suppress disulfide bond-dependent MLKL polymer formation and necroptosis. J. Biol. Chem. 292, 17514\u201317524 (2017).","journal-title":"J. Biol. Chem."},{"key":"1002_CR177","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7282","volume":"6","author":"KE Lawlor","year":"2015","unstructured":"Lawlor, K. E. et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat. Commun. 6, 6282 (2015).","journal-title":"Nat. Commun."},{"key":"1002_CR178","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1126\/science.284.5421.1841","volume":"284","author":"T Schwartz","year":"1999","unstructured":"Schwartz, T., Rould, M. A., Lowenhaupt, K., Herbert, A. & Rich, A. Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA. Science 284, 1841\u20131845 (1999).","journal-title":"Science"},{"key":"1002_CR179","doi-asserted-by":"publisher","first-page":"e1665","DOI":"10.1002\/wrna.1665","volume":"13","author":"B Song","year":"2022","unstructured":"Song, B., Shiromoto, Y., Minakuchi, M. & Nishikura, K. The role of RNA editing enzyme ADAR1 in human disease. Wiley Interdiscip. Rev. RNA 13, e1665 (2022).","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"1002_CR180","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1126\/science.aac7049","volume":"349","author":"BJ Liddicoat","year":"2015","unstructured":"Liddicoat, B. J. et al. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349, 1115\u20131120 (2015).","journal-title":"Science"},{"key":"1002_CR181","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.cell.2017.12.038","volume":"172","author":"H Chung","year":"2018","unstructured":"Chung, H. et al. Human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172, 811\u2013824.e814 (2018).","journal-title":"Cell"},{"key":"1002_CR182","doi-asserted-by":"publisher","first-page":"109858","DOI":"10.1016\/j.celrep.2021.109858","volume":"37","author":"R Karki","year":"2021","unstructured":"Karki, R. et al. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep. 37, 109858 (2021).","journal-title":"Cell Rep."},{"key":"1002_CR183","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.immuni.2016.07.016","volume":"45","author":"S Alvarez-Diaz","year":"2016","unstructured":"Alvarez-Diaz, S. et al. The pseudokinase MLKL and the kinase RIPK3 have distinct roles in autoimmune disease caused by loss of death-receptor-induced apoptosis. Immunity 45, 513\u2013526 (2016).","journal-title":"Immunity"},{"key":"1002_CR184","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1136\/gutjnl-2014-307226","volume":"64","author":"C Gunther","year":"2015","unstructured":"Gunther, C. et al. Caspase-8 controls the gut response to microbial challenges by Tnf-\u03b1-dependent and independent pathways. Gut 64, 601\u2013610 (2015).","journal-title":"Gut"},{"key":"1002_CR185","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1084\/jem.20090616","volume":"206","author":"A Kovalenko","year":"2009","unstructured":"Kovalenko, A. et al. Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. J. Exp. Med. 206, 2161\u20132177 (2009).","journal-title":"J. Exp. Med."},{"key":"1002_CR186","doi-asserted-by":"publisher","first-page":"8169","DOI":"10.1073\/pnas.0812453106","volume":"106","author":"JW Yu","year":"2009","unstructured":"Yu, J. W., Jeffrey, P. D. & Shi, Y. Mechanism of procaspase-8 activation by c-FLIPL. Proc. Natl Acad. Sci. USA 106, 8169\u20138174 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR187","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.molcel.2011.06.011","volume":"43","author":"M Feoktistova","year":"2011","unstructured":"Feoktistova, M. et al. cIAPs block ripoptosome formation, a RIP1\/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol. Cell 43, 449\u2013463 (2011).","journal-title":"Mol. Cell"},{"key":"1002_CR188","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.molcel.2011.06.006","volume":"43","author":"T Tenev","year":"2011","unstructured":"Tenev, T. et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell 43, 432\u2013448 (2011).","journal-title":"Mol. Cell"},{"key":"1002_CR189","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.bbrc.2016.10.015","volume":"480","author":"R Shindo","year":"2016","unstructured":"Shindo, R., Yamazaki, S., Ohmuraya, M., Araki, K. & Nakano, H. Short form FLICE-inhibitory protein promotes TNF\u03b1-induced necroptosis in fibroblasts derived from CFLARs transgenic mice. Biochem. Biophys. Res. Commun. 480, 23\u201328 (2016).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"1002_CR190","doi-asserted-by":"publisher","first-page":"e2415992122","DOI":"10.1073\/pnas.2415992122","volume":"122","author":"JJP Shaw","year":"2025","unstructured":"Shaw, J. J. P., Guy, C., Tummers, B. & Green, D. R. FLIP(L) permits apoptotic and inflammatory signaling and inhibits necroptosis in mice without Caspase-8 oligomerization. Proc. Natl Acad. Sci. USA 122, e2415992122 (2025).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR191","doi-asserted-by":"publisher","first-page":"e2308079120","DOI":"10.1073\/pnas.2308079120","volume":"120","author":"W Sun","year":"2023","unstructured":"Sun, W. et al. Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death. Proc. Natl Acad. Sci. USA 120, e2308079120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR192","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.devcel.2016.04.018","volume":"37","author":"ML Goodall","year":"2016","unstructured":"Goodall, M. L. et al. The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev. Cell 37, 337\u2013349 (2016).","journal-title":"Dev. Cell"},{"issue":"Pt 3","key":"1002_CR193","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1099\/0022-1317-78-3-677","volume":"78","author":"S Kettle","year":"1997","unstructured":"Kettle, S. et al. Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does not prevent IL-1beta-induced fever. J. Gen. Virol. 78(Pt 3), 677\u2013685 (1997).","journal-title":"J. Gen. Virol."},{"key":"1002_CR194","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1128\/JVI.01803-07","volume":"82","author":"L Cicin-Sain","year":"2008","unstructured":"Cicin-Sain, L. et al. Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an antiapoptotic viral gene. J. Virol. 82, 2056\u20132064 (2008).","journal-title":"J. Virol."},{"key":"1002_CR195","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.chom.2015.01.003","volume":"17","author":"H Guo","year":"2015","unstructured":"Guo, H. et al. Herpes simplex virus suppresses necroptosis in human cells. Cell Host Microbe 17, 243\u2013251 (2015).","journal-title":"Cell Host Microbe"},{"key":"1002_CR196","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.chom.2015.01.002","volume":"17","author":"Z Huang","year":"2015","unstructured":"Huang, Z. et al. RIP1\/RIP3 binding to HSV-1 ICP6 initiates necroptosis to restrict virus propagation in mice. Cell Host Microbe 17, 229\u2013242 (2015).","journal-title":"Cell Host Microbe"},{"key":"1002_CR197","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.15252\/embr.201743947","volume":"18","author":"H Sridharan","year":"2017","unstructured":"Sridharan, H. et al. Murine cytomegalovirus IE3-dependent transcription is required for DAI\/ZBP1-mediated necroptosis. EMBO Rep. 18, 1429\u20131441 (2017).","journal-title":"EMBO Rep."},{"key":"1002_CR198","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191913","author":"M Devos","year":"2020","unstructured":"Devos, M. et al. Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20191913 (2020).","journal-title":"J. Exp. Med."},{"key":"1002_CR199","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0868-3","volume":"9","author":"H Guo","year":"2018","unstructured":"Guo, H. et al. Species-independent contribution of ZBP1\/DAI\/DLM-1-triggered necroptosis in host defense against HSV1. Cell Death Dis. 9, 816 (2018).","journal-title":"Cell Death Dis."},{"key":"1002_CR200","doi-asserted-by":"publisher","first-page":"e1008473","DOI":"10.1371\/journal.ppat.1008473","volume":"16","author":"M Steain","year":"2020","unstructured":"Steain, M. et al. Varicella zoster virus encodes a viral decoy RHIM to inhibit cell death. PLoS Pathog. 16, e1008473 (2020).","journal-title":"PLoS Pathog."},{"key":"1002_CR201","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/j.celrep.2016.05.032","volume":"15","author":"D Legarda","year":"2016","unstructured":"Legarda, D. et al. CYLD proteolysis protects macrophages from TNF-mediated auto-necroptosis induced by LPS and licensed by type I IFN. Cell Rep. 15, 2449\u20132461 (2016).","journal-title":"Cell Rep."},{"key":"1002_CR202","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1126\/science.aay3878","volume":"367","author":"HI Muendlein","year":"2020","unstructured":"Muendlein, H. I. et al. cFLIP(L) protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation. Science 367, 1379\u20131384 (2020).","journal-title":"Science"},{"key":"1002_CR203","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1038\/ncb2362","volume":"13","author":"MA O\u2019Donnell","year":"2011","unstructured":"O\u2019Donnell, M. A. et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat. Cell Biol. 13, 1437\u20131442 (2011).","journal-title":"Nat. Cell Biol."},{"key":"1002_CR204","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1126\/science.aaf6803","volume":"353","author":"Y Ito","year":"2016","unstructured":"Ito, Y. et al. RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science 353, 603\u2013608 (2016).","journal-title":"Science"},{"key":"1002_CR205","doi-asserted-by":"publisher","first-page":"109112","DOI":"10.1016\/j.celrep.2021.109112","volume":"35","author":"M Zelic","year":"2021","unstructured":"Zelic, M. et al. RIPK1 activation mediates neuroinflammation and disease progression in multiple sclerosis. Cell Rep. 35, 109112 (2021).","journal-title":"Cell Rep."},{"key":"1002_CR206","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/nn.4608","volume":"20","author":"A Caccamo","year":"2017","unstructured":"Caccamo, A. et al. Necroptosis activation in Alzheimer\u2019s disease. Nat. Neurosci. 20, 1236\u20131246 (2017).","journal-title":"Nat. Neurosci."},{"key":"1002_CR207","doi-asserted-by":"publisher","first-page":"E8788","DOI":"10.1073\/pnas.1714175114","volume":"114","author":"D Ofengeim","year":"2017","unstructured":"Ofengeim, D. et al. RIPK1 mediates a disease-associated microglial response in Alzheimer\u2019s disease. Proc. Natl Acad. Sci. USA 114, E8788\u2013E8797 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR208","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41575-020-0326-4","volume":"17","author":"JV Patankar","year":"2020","unstructured":"Patankar, J. V. & Becker, C. Cell death in the gut epithelium and implications for chronic inflammation. Nat. Rev. Gastroenterol. Hepatol. 17, 543\u2013556 (2020).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1002_CR209","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1053\/j.gastro.2022.08.040","volume":"163","author":"SP Preston","year":"2022","unstructured":"Preston, S. P. et al. Epigenetic silencing of RIPK3 in hepatocytes prevents MLKL-mediated necroptosis from contributing to liver pathologies. Gastroenterology 163, 1643\u20131657.e1614 (2022).","journal-title":"Gastroenterology"},{"key":"1002_CR210","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05794-0","volume":"14","author":"J Hoff","year":"2023","unstructured":"Hoff, J. et al. RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis. Cell Death Dis. 14, 275 (2023).","journal-title":"Cell Death Dis."},{"key":"1002_CR211","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.immuni.2017.06.001","volume":"47","author":"S Yoon","year":"2017","unstructured":"Yoon, S., Kovalenko, A., Bogdanov, K. & Wallach, D. MLKL, the protein that mediates necroptosis, also regulates endosomal trafficking and extracellular vesicle generation. Immunity 47, 51\u201365.e57 (2017).","journal-title":"Immunity"},{"key":"1002_CR212","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaw3423","author":"W Fan","year":"2019","unstructured":"Fan, W. et al. Flotillin-mediated endocytosis and ALIX-syntenin-1-mediated exocytosis protect the cell membrane from damage caused by necroptosis. Sci. Signal. https:\/\/doi.org\/10.1126\/scisignal.aaw3423 (2019).","journal-title":"Sci. Signal."},{"key":"1002_CR213","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.cell.2017.03.020","volume":"169","author":"YN Gong","year":"2017","unstructured":"Gong, Y. N. et al. ESCRT-III acts downstream of MLKL to regulate necroptotic cell death and its consequences. Cell 169, 286\u2013300.e216 (2017).","journal-title":"Cell"},{"key":"1002_CR214","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1016\/j.celrep.2015.02.051","volume":"10","author":"D Ofengeim","year":"2015","unstructured":"Ofengeim, D. et al. Activation of necroptosis in multiple sclerosis. Cell Rep. 10, 1836\u20131849 (2015).","journal-title":"Cell Rep."},{"key":"1002_CR215","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s00401-021-02274-7","volume":"141","author":"C Picon","year":"2021","unstructured":"Picon, C. et al. Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter. Acta Neuropathol. 141, 585\u2013604 (2021).","journal-title":"Acta Neuropathol."},{"key":"1002_CR216","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/s41418-019-0408-4","volume":"27","author":"M Onate","year":"2020","unstructured":"Onate, M. et al. The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease. Cell Death Differ. 27, 1169\u20131185 (2020).","journal-title":"Cell Death Differ."},{"key":"1002_CR217","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04049-0","volume":"12","author":"TW Chou","year":"2021","unstructured":"Chou, T. W. et al. Fibrillar \u03b1-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-\u03baB. Cell Death Dis. 12, 756 (2021).","journal-title":"Cell Death Dis."},{"key":"1002_CR218","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1126\/science.abp9556","volume":"381","author":"S Balusu","year":"2023","unstructured":"Balusu, S. et al. MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer\u2019s disease. Science 381, 1176\u20131182 (2023).","journal-title":"Science"},{"key":"1002_CR219","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1385\/NMM:2:3:289","volume":"2","author":"A Suram","year":"2002","unstructured":"Suram, A., Rao, K. S., Latha, K. S. & Viswamitra, M. A. First evidence to show the topological change of DNA from B-dNA to Z-DNA conformation in the hippocampus of Alzheimer\u2019s brain. Neuromolecular Med. 2, 289\u2013297 (2002).","journal-title":"Neuromolecular Med."},{"key":"1002_CR220","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41392-023-01713-z","volume":"8","author":"J Wei","year":"2023","unstructured":"Wei, J. et al. Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis. Signal Transduct. Target. Ther. 8, 451 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"1002_CR221","doi-asserted-by":"publisher","first-page":"e27692","DOI":"10.7554\/eLife.27692","volume":"6","author":"D Li","year":"2017","unstructured":"Li, D. et al. RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system. eLife 6, e27692 (2017).","journal-title":"eLife"},{"key":"1002_CR222","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-07242-z","volume":"15","author":"S Chiou","year":"2024","unstructured":"Chiou, S. et al. MLKL deficiency elevates testosterone production in male mice independently of necroptotic functions. Cell Death Dis. 15, 851 (2024).","journal-title":"Cell Death Dis."},{"key":"1002_CR223","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1038\/s41418-023-01121-4","volume":"30","author":"EC Tovey Crutchfield","year":"2023","unstructured":"Tovey Crutchfield, E. C. et al. MLKL deficiency protects against low-grade, sterile inflammation in aged mice. Cell Death Differ. 30, 1059\u20131071 (2023).","journal-title":"Cell Death Differ."},{"key":"1002_CR224","doi-asserted-by":"publisher","first-page":"483","DOI":"10.21037\/apm.2019.07.04","volume":"8","author":"T Wu","year":"2019","unstructured":"Wu, T. et al. Expression of receptor interacting protein 3 and mixed lineage kinase domain-like protein-key proteins in necroptosis is upregulated in ulcerative colitis. Ann. Palliat. Med. 8, 483\u2013489 (2019).","journal-title":"Ann. Palliat. Med."},{"key":"1002_CR225","doi-asserted-by":"publisher","first-page":"113751","DOI":"10.1016\/j.bcp.2019.113751","volume":"172","author":"H Lu","year":"2020","unstructured":"Lu, H. et al. RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk. Biochem. Pharmacol. 172, 113751 (2020).","journal-title":"Biochem. Pharmacol."},{"key":"1002_CR226","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.4110\/in.2020.20.e16","volume":"20","author":"SH Lee","year":"2020","unstructured":"Lee, S. H. et al. Inhibition of RIPK3 pathway attenuates intestinal inflammation and cell death of inflammatory bowel disease and suppresses necroptosis in peripheral mononuclear cells of ulcerative colitis patients. Immune Netw. 20, e16 (2020).","journal-title":"Immune Netw."},{"key":"1002_CR227","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12876-022-02208-x","volume":"22","author":"C Duan","year":"2022","unstructured":"Duan, C., Xu, X., Lu, X., Wang, L. & Lu, Z. RIP3 knockdown inhibits necroptosis of human intestinal epithelial cells via TLR4\/MyD88\/NF-\u03baB signaling and ameliorates murine colitis. BMC Gastroenterol. 22, 137 (2022).","journal-title":"BMC Gastroenterol."},{"key":"1002_CR228","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/ajg.2013.403","volume":"109","author":"M Pierdomenico","year":"2014","unstructured":"Pierdomenico, M. et al. Necroptosis is active in children with inflammatory bowel disease and contributes to heighten intestinal inflammation. Am. J. Gastroenterol. 109, 279\u2013287 (2014).","journal-title":"Am. J. Gastroenterol."},{"key":"1002_CR229","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/s41418-020-00668-w","volume":"28","author":"L Tao","year":"2021","unstructured":"Tao, L. et al. RIP1 kinase activity promotes steatohepatitis through mediating cell death and inflammation in macrophages. Cell Death Differ. 28, 1418\u20131433 (2021).","journal-title":"Cell Death Differ."},{"key":"1002_CR230","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.jhep.2019.11.008","volume":"72","author":"A Majdi","year":"2020","unstructured":"Majdi, A. et al. Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease. J. Hepatol. 72, 627\u2013635 (2020).","journal-title":"J. Hepatol."},{"key":"1002_CR231","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38371-2","volume":"14","author":"T Zhang","year":"2023","unstructured":"Zhang, T. et al. UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis. Nat. Commun. 14, 2715 (2023).","journal-title":"Nat. Commun."},{"key":"1002_CR232","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1038\/cdd.2016.46","volume":"23","author":"K Newton","year":"2016","unstructured":"Newton, K. et al. RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury. Cell Death Differ. 23, 1565\u20131576 (2016).","journal-title":"Cell Death Differ."},{"key":"1002_CR233","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1053\/j.gastro.2018.09.041","volume":"156","author":"AS Lehle","year":"2019","unstructured":"Lehle, A. S. et al. Intestinal inflammation and dysregulated immunity in patients with inherited caspase-8 deficiency. Gastroenterology 156, 275\u2013278 (2019).","journal-title":"Gastroenterology"},{"key":"1002_CR234","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/s41418-024-01321-6","volume":"31","author":"L Koerner","year":"2024","unstructured":"Koerner, L. et al. ZBP1 causes inflammation by inducing RIPK3-mediated necroptosis and RIPK1 kinase activity-independent apoptosis. Cell Death Differ. 31, 938\u2013953 (2024).","journal-title":"Cell Death Differ."},{"key":"1002_CR235","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1038\/ng.2414","volume":"44","author":"GI Rice","year":"2012","unstructured":"Rice, G. I. et al. Mutations in ADAR1 cause Aicardi-Gouti\u00e8res syndrome associated with a type I interferon signature. Nat. Genet. 44, 1243\u20131248 (2012).","journal-title":"Nat. Genet."},{"key":"1002_CR236","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.64","volume":"3","author":"DE Christofferson","year":"2012","unstructured":"Christofferson, D. E. et al. A novel role for RIP1 kinase in mediating TNF\u03b1 production. Cell Death Dis. 3, e320 (2012).","journal-title":"Cell Death Dis."},{"key":"1002_CR237","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.molcel.2014.10.021","volume":"56","author":"P Mandal","year":"2014","unstructured":"Mandal, P. et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol. Cell 56, 481\u2013495 (2014).","journal-title":"Mol. Cell"},{"key":"1002_CR238","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/s41586-024-07265-8","volume":"628","author":"A Gautam","year":"2024","unstructured":"Gautam, A. et al. Necroptosis blockade prevents lung injury in severe influenza. Nature 628, 835\u2013843 (2024).","journal-title":"Nature"},{"key":"1002_CR239","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-020-0071-y","volume":"19","author":"L Mifflin","year":"2020","unstructured":"Mifflin, L., Ofengeim, D. & Yuan, J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat. Rev. Drug. Discov. 19, 553\u2013571 (2020).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"1002_CR240","doi-asserted-by":"publisher","first-page":"9714","DOI":"10.1073\/pnas.1901179116","volume":"116","author":"A Degterev","year":"2019","unstructured":"Degterev, A., Ofengeim, D. & Yuan, J. Targeting RIPK1 for the treatment of human diseases. Proc. Natl Acad. Sci. USA 116, 9714\u20139722 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR241","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","volume":"20","author":"J Yuan","year":"2019","unstructured":"Yuan, J., Amin, P. & Ofengeim, D. Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases. Nat. Rev. Neurosci. 20, 19\u201333 (2019).","journal-title":"Nat. Rev. Neurosci."},{"key":"1002_CR242","doi-asserted-by":"publisher","first-page":"1159743","DOI":"10.3389\/fimmu.2023.1159743","volume":"14","author":"W Li","year":"2023","unstructured":"Li, W. & Yuan, J. Targeting RIPK1 kinase for modulating inflammation in human diseases. Front. Immunol. 14, 1159743 (2023).","journal-title":"Front. Immunol."},{"key":"1002_CR243","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.365","author":"K Weisel","year":"2017","unstructured":"Weisel, K. et al. Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers. Pharmacol. Res. Perspect. https:\/\/doi.org\/10.1002\/prp2.365 (2017).","journal-title":"Pharmacol. Res. Perspect."},{"key":"1002_CR244","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2021-000680","author":"K Weisel","year":"2021","unstructured":"Weisel, K. et al. A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis. BMJ Open Gastroenterol. https:\/\/doi.org\/10.1136\/bmjgast-2021-000680 (2021).","journal-title":"BMJ Open Gastroenterol."},{"key":"1002_CR245","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s13075-021-02468-0","volume":"23","author":"K Weisel","year":"2021","unstructured":"Weisel, K. et al. A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis. Arthritis Res. Ther. 23, 85 (2021).","journal-title":"Arthritis Res. Ther."},{"key":"1002_CR246","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1002\/cpt.1852","volume":"108","author":"K Weisel","year":"2020","unstructured":"Weisel, K. et al. Response to inhibition of receptor-interacting protein kinase 1 (RIPK1) in active plaque psoriasis: a randomized placebo-controlled study. Clin. Pharmacol. Ther. 108, 808\u2013816 (2020).","journal-title":"Clin. Pharmacol. Ther."},{"key":"1002_CR247","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1111\/cts.13317","volume":"15","author":"M Vissers","year":"2022","unstructured":"Vissers, M. et al. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: randomized, placebo-controlled, double-blind phase I\/Ib studies in healthy subjects and patients. Clin. Transl. Sci. 15, 2010\u20132023 (2022).","journal-title":"Clin. Transl. Sci."},{"key":"1002_CR248","doi-asserted-by":"publisher","first-page":"e13857","DOI":"10.1111\/cts.13857","volume":"17","author":"ALA Sun","year":"2024","unstructured":"Sun, A. L. A. et al. A phase I randomized study to evaluate safety, pharmacokinetics, and pharmacodynamics of SIR2446M, a selective RIPK1 inhibitor, in healthy participants. Clin. Transl. Sci. 17, e13857 (2024).","journal-title":"Clin. Transl. Sci."},{"key":"1002_CR249","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s13555-024-01097-0","volume":"14","author":"VJ Ludbrook","year":"2024","unstructured":"Ludbrook, V. J. et al. Inhibition of receptor-interacting protein kinase 1 in chronic plaque psoriasis: a multicenter, randomized, double-blind, placebo-controlled study. Dermatol. Ther. 14, 489\u2013504 (2024).","journal-title":"Dermatol. Ther."},{"key":"1002_CR250","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1111\/cts.13580","volume":"16","author":"J Lickliter","year":"2023","unstructured":"Lickliter, J. et al. A phase I randomized, double-blinded, placebo-controlled study assessing the safety and pharmacokinetics of RIPK1 inhibitor GFH312 in healthy subjects. Clin. Transl. Sci. 16, 1691\u20131703 (2023).","journal-title":"Clin. Transl. Sci."},{"key":"1002_CR251","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1111\/cts.13607","volume":"16","author":"NS Jones","year":"2023","unstructured":"Jones, N. S. et al. A phase I, randomized, ascending-dose study to assess safety, pharmacokinetics, and activity of GDC-8264, a RIP1 inhibitor, in healthy volunteers. Clin. Transl. Sci. 16, 1997\u20132009 (2023).","journal-title":"Clin. Transl. Sci."},{"key":"1002_CR252","doi-asserted-by":"publisher","first-page":"e13690","DOI":"10.1111\/cts.13690","volume":"17","author":"A Hincelin-Mery","year":"2024","unstructured":"Hincelin-Mery, A. et al. Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants. Clin. Transl. Sci. 17, e13690 (2024).","journal-title":"Clin. Transl. Sci."},{"key":"1002_CR253","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/s41418-020-00690-y","volume":"28","author":"T Riebeling","year":"2021","unstructured":"Riebeling, T. et al. Primidone blocks RIPK1-driven cell death and inflammation. Cell Death Differ. 28, 1610\u20131626 (2021).","journal-title":"Cell Death Differ."},{"key":"1002_CR254","doi-asserted-by":"publisher","first-page":"e2005756","DOI":"10.1371\/journal.pbio.2005756","volume":"16","author":"A Najafov","year":"2018","unstructured":"Najafov, A. et al. BRAF and AXL oncogenes drive RIPK3 expression loss in cancer. PLoS Biol. 16, e2005756 (2018).","journal-title":"PLoS Biol."},{"key":"1002_CR255","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1016\/j.immuni.2024.04.025","volume":"57","author":"J Mannion","year":"2024","unstructured":"Mannion, J. et al. A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death. Immunity 57, 1514\u20131532.e1515 (2024).","journal-title":"Immunity"},{"key":"1002_CR256","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55006-2","volume":"15","author":"X Yu","year":"2024","unstructured":"Yu, X. et al. Development of a RIPK1 degrader to enhance antitumor immunity. Nat. Commun. 15, 10683 (2024).","journal-title":"Nat. Commun."},{"key":"1002_CR257","doi-asserted-by":"publisher","first-page":"116384","DOI":"10.1016\/j.celrep.2025.116384","volume":"44","author":"X Jiang","year":"2025","unstructured":"Jiang, X. et al. Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer. Cell Rep. 44, 116384 (2025).","journal-title":"Cell Rep."},{"key":"1002_CR258","doi-asserted-by":"publisher","first-page":"61","DOI":"10.15252\/emmm.201606566","volume":"9","author":"SH Yang","year":"2017","unstructured":"Yang, S. H. et al. Nec-1 alleviates cognitive impairment with reduction of A\u03b2 and tau abnormalities in APP\/PS1 mice. EMBO Mol. Med. 9, 61\u201377 (2017).","journal-title":"EMBO Mol. Med."},{"key":"1002_CR259","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40478-022-01332-9","volume":"10","author":"N Salvadores","year":"2022","unstructured":"Salvadores, N. et al. A\u03b2 oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer\u2019s disease. Acta Neuropathol. Commun. 10, 31 (2022).","journal-title":"Acta Neuropathol. Commun."},{"key":"1002_CR260","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41374-019-0319-5","volume":"100","author":"QS Lin","year":"2020","unstructured":"Lin, Q. S. et al. RIP1\/RIP3\/MLKL mediates dopaminergic neuron necroptosis in a mouse model of Parkinson disease. Lab. Invest. 100, 503\u2013511 (2020).","journal-title":"Lab. Invest."},{"key":"1002_CR261","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1016\/j.celrep.2018.01.089","volume":"22","author":"A Iannielli","year":"2018","unstructured":"Iannielli, A. et al. Pharmacological inhibition of necroptosis protects from dopaminergic neuronal cell death in Parkinson\u2019s disease models. Cell Rep. 22, 2066\u20132079 (2018).","journal-title":"Cell Rep."},{"key":"1002_CR262","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41420-022-00929-2","volume":"8","author":"XR Ma","year":"2022","unstructured":"Ma, X. R. et al. Inhibition of RIPK1 by ZJU-37 promotes oligodendrocyte progenitor proliferation and remyelination via NF-\u03baB pathway. Cell Death Discov. 8, 147 (2022).","journal-title":"Cell Death Discov."},{"key":"1002_CR263","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.dld.2017.08.017","volume":"49","author":"A Negroni","year":"2017","unstructured":"Negroni, A. et al. RIP3 AND pMLKL promote necroptosis-induced inflammation and alter membrane permeability in intestinal epithelial cells. Dig. Liver Dis. 49, 1201\u20131210 (2017).","journal-title":"Dig. Liver Dis."},{"key":"1002_CR264","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.molimm.2019.01.018","volume":"107","author":"J Zhang","year":"2019","unstructured":"Zhang, J. et al. MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota. Mol. Immunol. 107, 132\u2013141 (2019).","journal-title":"Mol. Immunol."},{"key":"1002_CR265","doi-asserted-by":"publisher","first-page":"12024","DOI":"10.1073\/pnas.1305538110","volume":"110","author":"A Linkermann","year":"2013","unstructured":"Linkermann, A. et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc. Natl Acad. Sci. USA 110, 12024\u201312029 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR266","doi-asserted-by":"publisher","first-page":"109262","DOI":"10.1016\/j.intimp.2022.109262","volume":"112","author":"CH Xu","year":"2022","unstructured":"Xu, C. H. et al. RIPK3 inhibitor-AZD5423 alleviates acute kidney injury by inhibiting necroptosis and inflammation. Int. Immunopharmacol. 112, 109262 (2022).","journal-title":"Int. Immunopharmacol."},{"key":"1002_CR267","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1111\/ajt.12447","volume":"13","author":"A Lau","year":"2013","unstructured":"Lau, A. et al. RIPK3-mediated necroptosis promotes donor kidney inflammatory injury and reduces allograft survival. Am. J. Transplant. 13, 2805\u20132818 (2013).","journal-title":"Am. J. Transplant."},{"key":"1002_CR268","doi-asserted-by":"publisher","first-page":"4182","DOI":"10.1073\/pnas.1716578115","volume":"115","author":"D Martin-Sanchez","year":"2018","unstructured":"Martin-Sanchez, D. et al. TWEAK and RIPK1 mediate a second wave of cell death during AKI. Proc. Natl Acad. Sci. USA 115, 4182\u20134187 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1002_CR269","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98411","author":"A Sureshbabu","year":"2018","unstructured":"Sureshbabu, A. et al. RIPK3 promotes sepsis-induced acute kidney injury via mitochondrial dysfunction. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.98411 (2018).","journal-title":"JCI Insight"},{"key":"1002_CR270","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0936-8","volume":"9","author":"H Chen","year":"2018","unstructured":"Chen, H. et al. RIPK3-MLKL-mediated necroinflammation contributes to AKI progression to CKD. Cell Death Dis. 9, 878 (2018).","journal-title":"Cell Death Dis."},{"key":"1002_CR271","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.omtn.2019.06.025","volume":"17","author":"B Shen","year":"2019","unstructured":"Shen, B. et al. Necrostatin-1 attenuates renal ischemia and reperfusion injury via meditation of HIF-1\u03b1\/mir-26a\/TRPC6\/PARP1 signaling. Mol. Ther. Nucleic Acids 17, 701\u2013713 (2019).","journal-title":"Mol. Ther. Nucleic Acids"}],"updated-by":[{"DOI":"10.1038\/s41580-026-01022-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000}}],"container-title":["Nature Reviews Molecular Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41580-026-01002-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41580-026-01002-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41580-026-01002-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:08:28Z","timestamp":1789992508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41580-026-01002-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":271,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["1002"],"URL":"https:\/\/doi.org\/10.1038\/s41580-026-01002-x","relation":{},"ISSN":["1471-0072","1471-0080"],"issn-type":[{"value":"1471-0072","type":"print"},{"value":"1471-0080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"18 June 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2026","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41580-026-01022-7","URL":"https:\/\/doi.org\/10.1038\/s41580-026-01022-7","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}