{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:24:12Z","timestamp":1790619852118,"version":"4.1.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS091080"],"award-info":[{"award-number":["NS091080"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS099175"],"award-info":[{"award-number":["NS099175"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012380","name":"Cleveland Clinic | Lerner Research Institute, Cleveland Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"HHS | NIH | Office of Research Infrastructure Programs, National Institutes of Health","doi-asserted-by":"publisher","award":["1S10RR031536\u201001"],"award-info":[{"award-number":["1S10RR031536\u201001"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"HHS | NIH | Office of Research Infrastructure Programs, National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD018205"],"award-info":[{"award-number":["S10OD018205"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2022,4,4]]},"DOI":"10.15252\/embj.2021109187","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T07:14:34Z","timestamp":1645514074000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["USP33 deubiquitinates and stabilizes HIF\u20102alpha to promote hypoxia response in glioma stem cells"],"prefix":"10.1038","volume":"41","author":[{"given":"Aili","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy N","family":"Rich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-1831","authenticated-orcid":false,"given":"Wenchao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4236-2662","authenticated-orcid":false,"given":"Shideng","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"BFEMBJ2021109187_CR1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.cell.2008.06.048","volume":"134","author":"G Alexandru","year":"2008","unstructured":"Alexandru G, Graumann J, Smith GT, Kolawa NJ, Fang R, Deshaies RJ (2008) UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover. Cell 134: 804\u2013816","journal-title":"Cell"},{"key":"BFEMBJ2021109187_CR2","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1074\/jbc.M111.305615","volume":"287","author":"M Altun","year":"2012","unstructured":"Altun M, Zhao B, Velasco K, Liu H, Hassink G, Paschke J, Pereira T, Lindsten K (2012) Ubiquitin\u2010specific protease 19 (USP19) regulates hypoxia\u2010inducible factor 1alpha (HIF\u20101alpha) during hypoxia. J Biol Chem 287: 1962\u20131969","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR3","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/nature05236","volume":"444","author":"S Bao","year":"2006","unstructured":"Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756\u2013760","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR4","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/emboj.2009.128","volume":"28","author":"M Berthouze","year":"2009","unstructured":"Berthouze M, Venkataramanan V, Li Y, Shenoy SK (2009) The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J 28: 1684\u20131696","journal-title":"EMBO J"},{"key":"BFEMBJ2021109187_CR5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1042\/BJ20130026","volume":"451","author":"JS Bett","year":"2013","unstructured":"Bett JS, Ibrahim AF, Garg AK, Kelly V, Pedrioli P, Rocha S, Hay RT (2013) The P\u2010body component USP52\/PAN2 is a novel regulator of HIF1A mRNA stability. Biochem J 451: 185\u2013194","journal-title":"Biochem J"},{"key":"BFEMBJ2021109187_CR6","first-page":"4693","volume":"60","author":"P Birner","year":"2000","unstructured":"Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G (2000) Overexpression of hypoxia\u2010inducible factor 1alpha is a marker for an unfavorable prognosis in early\u2010stage invasive cervical cancer. Cancer Res 60: 4693\u20134696","journal-title":"Cancer Res"},{"key":"BFEMBJ2021109187_CR7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ccr.2011.11.017","volume":"21","author":"C Branco\u2010Price","year":"2012","unstructured":"Branco\u2010Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, Ellies L, Johnson RS (2012) Endothelial cell HIF\u20101alpha and HIF\u20102alpha differentially regulate metastatic success. Cancer Cell 21: 52\u201365","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR8","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.15252\/embr.201438850","volume":"15","author":"A Bremm","year":"2014","unstructured":"Bremm A, Moniz S, Mader J, Rocha S, Komander D (2014) Cezanne (OTUD7B) regulates HIF\u20101alpha homeostasis in a proteasome\u2010independent manner. EMBO Rep 15: 1268\u20131277","journal-title":"EMBO Rep"},{"key":"BFEMBJ2021109187_CR10","doi-asserted-by":"crossref","first-page":"19789","DOI":"10.1074\/jbc.M114.569392","volume":"289","author":"NC Chan","year":"2014","unstructured":"Chan NC, den Besten W, Sweredoski MJ, Hess S, Deshaies RJ, Chan DC (2014) Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2. J Biol Chem 289: 19789\u201319798","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR12","doi-asserted-by":"crossref","first-page":"32116","DOI":"10.1074\/jbc.M110.131284","volume":"285","author":"YK Choi","year":"2010","unstructured":"Choi YK, Kim CK, Lee H, Jeoung D, Ha KS, Kwon YG, Kim KW, Kim YM (2010) Carbon monoxide promotes VEGF expression by increasing HIF\u20101alpha protein level via two distinct mechanisms, translational activation and stabilization of HIF\u20101alpha protein. J Biol Chem 285: 32116\u201332125","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR13","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41580-019-0099-1","volume":"20","author":"MJ Clague","year":"2019","unstructured":"Clague MJ, Urbe S, Komander D (2019) Breaking the chains: deubiquitylating enzyme specificity begets function. Nat Rev Mol Cell Biol 20: 338\u2013352","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBJ2021109187_CR14","doi-asserted-by":"crossref","first-page":"33709","DOI":"10.1074\/jbc.274.47.33709","volume":"274","author":"PW Conrad","year":"1999","unstructured":"Conrad PW, Freeman TL, Beitner\u2010Johnson D, Millhorn DE (1999) EPAS1 trans\u2010activation during hypoxia requires p42\/p44 MAPK. J Biol Chem 274: 33709\u201333713","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR15","first-page":"949","volume":"72","author":"MR Doe","year":"2012","unstructured":"Doe MR, Ascano JM, Kaur M, Cole MD (2012) Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res 72: 949\u2013957","journal-title":"Cancer Res"},{"key":"BFEMBJ2021109187_CR16","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00401-013-1142-5","volume":"126","author":"TR Doeppner","year":"2013","unstructured":"Doeppner TR, Doehring M, Bretschneider E, Zechariah A, Kaltwasser B, Muller B, Koch JC, Bahr M, Hermann DM, Michel U (2013) MicroRNA\u2010124 protects against focal cerebral ischemia via mechanisms involving Usp14\u2010dependent REST degradation. Acta Neuropathol 126: 251\u2013265","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2021109187_CR17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/ncb2954","volume":"16","author":"Y Fan","year":"2014","unstructured":"Fan Y, Potdar AA, Gong Y, Eswarappa SM, Donnola S, Lathia JD, Hambardzumyan D, Rich JN, Fox PL (2014) Profilin\u20101 phosphorylation directs angiocrine expression and glioblastoma progression through HIF\u20101alpha accumulation. Nat Cell Biol 16: 445\u2013456","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2021109187_CR18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1084\/jem.20151673","volume":"214","author":"X Fang","year":"2017","unstructured":"Fang X, Zhou W, Wu Q, Huang Z, Shi YU, Yang K, Chen C, Xie QI, Mack SC, Wang X et\u00a0al (2017) Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14\u2010mediated Myc ubiquitination. J Exp Med 214: 245\u2013267","journal-title":"J Exp Med"},{"key":"BFEMBJ2021109187_CR19","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.4161\/cc.25035","volume":"12","author":"M Faronato","year":"2013","unstructured":"Faronato M, Patel V, Darling S, Dearden L, Clague MJ, Urbe S, Coulson JM (2013) The deubiquitylase USP15 stabilizes newly synthesized REST and rescues its expression at mitotic exit. Cell Cycle 12: 1964\u20131977","journal-title":"Cell Cycle"},{"key":"BFEMBJ2021109187_CR20","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/ncb3465","volume":"19","author":"G Fluegen","year":"2017","unstructured":"Fluegen G, Avivar\u2010Valderas A, Wang Y, Padgen MR, Williams JK, Nobre A, Calvo V, Cheung JF, Bravo\u2010Cordero JJ, Entenberg D et\u00a0al (2017) Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nat Cell Biol 19: 120\u2013132","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2021109187_CR21","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1182\/blood-2011-08-375014","volume":"119","author":"D Flugel","year":"2012","unstructured":"Flugel D, Gorlach A, Kietzmann T (2012) GSK\u20103beta regulates cell growth, migration, and angiogenesis via Fbw7 and USP28\u2010dependent degradation of HIF\u20101alpha. Blood 119: 1292\u20131301","journal-title":"Blood"},{"key":"BFEMBJ2021109187_CR22","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","volume":"16","author":"JA Forsythe","year":"1996","unstructured":"Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia\u2010inducible factor 1. Mol Cell Biol 16: 4604\u20134613","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021109187_CR23","doi-asserted-by":"crossref","first-page":"21306","DOI":"10.1073\/pnas.0906432106","volume":"106","author":"A Franovic","year":"2009","unstructured":"Franovic A, Holterman CE, Payette J, Lee S (2009) Human cancers converge at the HIF\u20102alpha oncogenic axis. Proc Natl Acad Sci USA 106: 21306\u201321311","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2021109187_CR24","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1054\/bjoc.2001.2018","volume":"85","author":"A Giatromanolaki","year":"2001","unstructured":"Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Talks K, Pezzella F, Gatter KC, Harris AL (2001) Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non\u2010small cell lung cancer to angiogenic\/molecular profile of tumours and survival. Br J Cancer 85: 881\u2013890","journal-title":"Br J Cancer"},{"key":"BFEMBJ2021109187_CR25","doi-asserted-by":"crossref","first-page":"jcs225698","DOI":"10.1242\/jcs.225698","volume":"132","author":"IM Gkotinakou","year":"2019","unstructured":"Gkotinakou IM, Befani C, Simos G, Liakos P (2019) ERK1\/2 phosphorylates HIF\u20102alpha and regulates its activity by controlling its CRM1\u2010dependent nuclear shuttling. J Cell Sci 132: jcs225698","journal-title":"J Cell Sci"},{"key":"BFEMBJ2021109187_CR26","doi-asserted-by":"crossref","first-page":"22159","DOI":"10.1016\/S0021-9258(18)54548-8","volume":"266","author":"FA Gonzalez","year":"1991","unstructured":"Gonzalez FA, Raden DL, Davis RJ (1991) Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases. J Biol Chem 266: 22159\u201322163","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR27","doi-asserted-by":"crossref","first-page":"6153","DOI":"10.1038\/ncomms7153","volume":"6","author":"Y Goto","year":"2015","unstructured":"Goto Y, Zeng L, Yeom CJ, Zhu Y, Morinibu A, Shinomiya K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M et\u00a0al (2015) UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF\u20101alpha. Nat Commun 6: 6153","journal-title":"Nat Commun"},{"key":"BFEMBJ2021109187_CR28","doi-asserted-by":"crossref","first-page":"9212","DOI":"10.1158\/0008-5472.CAN-08-1135","volume":"68","author":"K Helczynska","year":"2008","unstructured":"Helczynska K, Larsson AM, Holmquist Mengelbier L, Bridges E, Fredlund E, Borgquist S, Landberg G, Pahlman S, Jirstrom K (2008) Hypoxia\u2010inducible factor\u20102alpha correlates to distant recurrence and poor outcome in invasive breast cancer. Cancer Res 68: 9212\u20139220","journal-title":"Cancer Res"},{"key":"BFEMBJ2021109187_CR29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ccr.2006.08.026","volume":"10","author":"L Holmquist\u2010Mengelbier","year":"2006","unstructured":"Holmquist\u2010Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H, Pietras A, Vallon\u2010Christersson J, Borg A, Gradin K et\u00a0al (2006) Recruitment of HIF\u20101alpha and HIF\u20102alpha to common target genes is differentially regulated in neuroblastoma: HIF\u20102alpha promotes an aggressive phenotype. Cancer Cell 10: 413\u2013423","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR30","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.1091\/mbc.e06-05-0419","volume":"18","author":"CJ Hu","year":"2007","unstructured":"Hu CJ, Sataur A, Wang L, Chen H, Simon MC (2007) The N\u2010terminal transactivation domain confers target gene specificity of hypoxia\u2010inducible factors HIF\u20101alpha and HIF\u20102alpha. Mol Biol Cell 18: 4528\u20134542","journal-title":"Mol Biol Cell"},{"key":"BFEMBJ2021109187_CR31","doi-asserted-by":"crossref","first-page":"9361","DOI":"10.1128\/MCB.23.24.9361-9374.2003","volume":"23","author":"CJ Hu","year":"2003","unstructured":"Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC (2003) Differential roles of hypoxia\u2010inducible factor 1alpha (HIF\u20101alpha) and HIF\u20102alpha in hypoxic gene regulation. Mol Cell Biol 23: 9361\u20139374","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021109187_CR32","doi-asserted-by":"crossref","first-page":"7987","DOI":"10.1073\/pnas.95.14.7987","volume":"95","author":"LE Huang","year":"1998","unstructured":"Huang LE, Gu J, Schau M, Bunn HF (1998) Regulation of hypoxia\u2010inducible factor 1alpha is mediated by an O2\u2010dependent degradation domain via the ubiquitin\u2010proteasome pathway. Proc Natl Acad Sci USA 95: 7987\u20137992","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2021109187_CR33","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ncb2153","volume":"13","author":"Z Huang","year":"2011","unstructured":"Huang Z, Wu Q, Guryanova OA, Cheng L, Shou W, Rich JN, Bao S (2011) Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. Nat Cell Biol 13: 142\u2013152","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2021109187_CR36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2008.04.009","volume":"30","author":"WG Kaelin Jr","year":"2008","unstructured":"Kaelin Jr WG, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30: 393\u2013402","journal-title":"Mol Cell"},{"key":"BFEMBJ2021109187_CR37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc3183","volume":"12","author":"B Keith","year":"2011","unstructured":"Keith B, Johnson RS, Simon MC (2011) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12: 9\u201322","journal-title":"Nat Rev Cancer"},{"key":"BFEMBJ2021109187_CR38","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1002\/jcp.25841","volume":"232","author":"D Kim","year":"2017","unstructured":"Kim D, Hong A, Park HI, Shin WH, Yoo L, Jeon SJ, Chung KC (2017) Deubiquitinating enzyme USP22 positively regulates c\u2010Myc stability and tumorigenic activity in mammalian and breast cancer cells. J Cell Physiol 232: 3664\u20133676","journal-title":"J Cell Physiol"},{"key":"BFEMBJ2021109187_CR39","doi-asserted-by":"crossref","first-page":"7388","DOI":"10.1158\/1078-0432.CCR-07-0411","volume":"13","author":"T Klatte","year":"2007","unstructured":"Klatte T, Seligson DB, Riggs SB, Leppert JT, Berkman MK, Kleid MD, Yu H, Kabbinavar FF, Pantuck AJ, Belldegrun AS (2007) Hypoxia\u2010inducible factor 1 alpha in clear cell renal cell carcinoma. Clin Cancer Res 13: 7388\u20137393","journal-title":"Clin Cancer Res"},{"key":"BFEMBJ2021109187_CR40","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1096\/fj.201701344RRR","volume":"32","author":"SB Kokate","year":"2018","unstructured":"Kokate SB, Dixit P, Das L, Rath S, Roy AD, Poirah I, Chakraborty D, Rout N, Singh SP, Bhattacharyya A (2018) Acetylation\u2010mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori\u2010infected gastric epithelial cancer cells. FASEB J 32: 5378\u20135389","journal-title":"FASEB J"},{"key":"BFEMBJ2021109187_CR41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S1535-6108(02)00043-0","volume":"1","author":"K Kondo","year":"2002","unstructured":"Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin Jr WG (2002) Inhibition of HIF is necessary for tumor suppression by the von Hippel\u2010Lindau protein. Cancer Cell 1: 237\u2013246","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR42","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/ncb3330","volume":"18","author":"EL LaGory","year":"2016","unstructured":"LaGory EL, Giaccia AJ (2016) The ever\u2010expanding role of HIF in tumour and stromal biology. Nat Cell Biol 18: 356\u2013365","journal-title":"Nat Cell Biol"},{"key":"BFEMBJ2021109187_CR43","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cell.2015.03.011","volume":"161","author":"D Lee","year":"2015","unstructured":"Lee D, Sohn H, Park Z\u2010Y, Oh S, Kang Y, Lee K\u2010M, Kang M, Jang Y, Yang S\u2010J, Hong Y et\u00a0al (2015) A lactate\u2010induced response to hypoxia. Cell 161: 595\u2013609","journal-title":"Cell"},{"key":"BFEMBJ2021109187_CR44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nature16475","volume":"529","author":"SB Lee","year":"2016","unstructured":"Lee SB, Frattini V, Bansal M, Castano AM, Sherman D, Hutchinson K, Bruce JN, Califano A, Liu G, Cardozo T et\u00a0al (2016) An ID2\u2010dependent mechanism for VHL inactivation in cancer. Nature 529: 172\u2013177","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR45","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nature11941","volume":"495","author":"J Li","year":"2013","unstructured":"Li J, D'Angiolella V, Seeley ES, Kim S, Kobayashi T, Fu W, Campos EI, Pagano M, Dynlacht BD (2013) USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110. Nature 495: 255\u2013259","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR46","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ccr.2013.12.008","volume":"25","author":"J Li","year":"2014","unstructured":"Li J, Xu Y, Long XD, Wang W, Jiao HK, Mei Z, Yin QQ, Ma LN, Zhou AW, Wang LS et\u00a0al (2014) Cbx4 governs HIF\u20101alpha to potentiate angiogenesis of hepatocellular carcinoma by its SUMO E3 ligase activity. Cancer Cell 25: 118\u2013131","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00401-008-0339-5","volume":"115","author":"L Li","year":"2008","unstructured":"Li L, Xiong Y, Qu Y, Mao M, Mu W, Wang H, Mu D (2008) The requirement of extracellular signal\u2010related protein kinase pathway in the activation of hypoxia inducible factor 1 alpha in the developing rat brain after hypoxia\u2010ischemia. Acta Neuropathol 115: 297\u2013303","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2021109187_CR49","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ccr.2009.03.018","volume":"15","author":"Z Li","year":"2009","unstructured":"Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE et\u00a0al (2009) Hypoxia\u2010inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15: 501\u2013513","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR50","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1074\/jbc.M108269200","volume":"277","author":"Z Li","year":"2002","unstructured":"Li Z, Na X, Wang D, Schoen SR, Messing EM, Wu G (2002) Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel\u2010Lindau tumor suppressor protein. J Biol Chem 277: 4656\u20134662","journal-title":"J Biol Chem"},{"key":"BFEMBJ2021109187_CR51","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/sj.embor.7400377","volume":"6","author":"Z Li","year":"2005","unstructured":"Li Z, Wang D, Messing EM, Wu G (2005) VHL protein\u2010interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF\u20101alpha. EMBO Rep 6: 373\u2013378","journal-title":"EMBO Rep"},{"key":"BFEMBJ2021109187_CR52","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/embor.2010.170","volume":"12","author":"C Loenarz","year":"2011","unstructured":"Loenarz C, Coleman ML, Boleininger A, Schierwater B, Holland PW, Ratcliffe PJ, Schofield CJ (2011) The hypoxia\u2010inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens. EMBO Rep 12: 63\u201370","journal-title":"EMBO Rep"},{"key":"BFEMBJ2021109187_CR53","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ccell.2019.08.007","volume":"36","author":"L Ma","year":"2019","unstructured":"Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, Rae Z, Hernandez JM, Davis JL, Martin SP et\u00a0al (2019) Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell 36: 418\u2013430","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR54","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.stem.2017.10.005","volume":"22","author":"J Man","year":"2018","unstructured":"Man J, Yu X, Huang H, Zhou W, Xiang C, Huang H, Miele L, Liu Z, Bebek G, Bao S et\u00a0al (2018) Hypoxic induction of vasorin regulates notch1 turnover to maintain glioma stem\u2010like cells. Cell Stem Cell 22: 104\u2013118","journal-title":"Cell Stem Cell"},{"key":"BFEMBJ2021109187_CR55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1126\/science.aaw0112","volume":"365","author":"N Masson","year":"2019","unstructured":"Masson N, Keeley TP, Giuntoli B, White MD, Puerta ML, Perata P, Hopkinson RJ, Flashman E, Licausi F, Ratcliffe PJ (2019) Conserved N\u2010terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. Science 365: 65\u201369","journal-title":"Science"},{"key":"BFEMBJ2021109187_CR56","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.1093\/emboj\/20.18.5197","volume":"20","author":"N Masson","year":"2001","unstructured":"Masson N, Willam C, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Independent function of two destruction domains in hypoxia\u2010inducible factor\u2010alpha chains activated by prolyl hydroxylation. EMBO J 20: 5197\u20135206","journal-title":"EMBO J"},{"key":"BFEMBJ2021109187_CR57","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.trecan.2019.08.005","volume":"5","author":"D Mennerich","year":"2019","unstructured":"Mennerich D, Kubaichuk K, Kietzmann T (2019) DUBs, hypoxia, and cancer. Trends Cancer 5: 632\u2013653","journal-title":"Trends Cancer"},{"key":"BFEMBJ2021109187_CR58","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0014-5793(00)01181-9","volume":"468","author":"E Minet","year":"2000","unstructured":"Minet E, Arnould T, Michel G, Roland I, Mottet D, Raes M, Remacle J, Michiels C (2000) ERK activation upon hypoxia: involvement in HIF\u20101 activation. FEBS Lett 468: 53\u201358","journal-title":"FEBS Lett"},{"key":"BFEMBJ2021109187_CR59","first-page":"3082","volume":"128","author":"S Moniz","year":"2015","unstructured":"Moniz S, Bandarra D, Biddlestone J, Campbell KJ, Komander D, Bremm A, Rocha S (2015) Cezanne regulates E2F1\u2010dependent HIF2alpha expression. J Cell Sci 128: 3082\u20133093","journal-title":"J Cell Sci"},{"key":"BFEMBJ2021109187_CR60","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/375577a0","volume":"375","author":"D Mukhopadhyay","year":"1995","unstructured":"Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP (1995) Hypoxic induction of human vascular endothelial growth factor expression through c\u2010Src activation. Nature 375: 577\u2013581","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR61","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1080\/15548627.2019.1656957","volume":"16","author":"K Niu","year":"2020","unstructured":"Niu K, Fang H, Chen Z, Zhu Y, Tan Q, Wei D, Li Y, Balajee AS, Zhao Y (2020) USP33 deubiquitinates PRKN\/parkin and antagonizes its role in mitophagy. Autophagy 16: 724\u2013734","journal-title":"Autophagy"},{"key":"BFEMBJ2021109187_CR62","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.humpath.2007.02.010","volume":"38","author":"R Osada","year":"2007","unstructured":"Osada R, Horiuchi A, Kikuchi N, Yoshida J, Hayashi A, Ota M, Katsuyama Y, Melillo G, Konishi I (2007) Expression of hypoxia\u2010inducible factor 1alpha, hypoxia\u2010inducible factor 2alpha, and von Hippel\u2010Lindau protein in epithelial ovarian neoplasms and allelic loss of von Hippel\u2010Lindau gene: nuclear expression of hypoxia\u2010inducible factor 1alpha is an independent prognostic factor in ovarian carcinoma. Hum Pathol 38: 1310\u20131320","journal-title":"Hum Pathol"},{"key":"BFEMBJ2021109187_CR63","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1158\/2159-8290.CD-11-0314","volume":"2","author":"A Palazon","year":"2012","unstructured":"Palazon A, Martinez\u2010Forero I, Teijeira A, Morales\u2010Kastresana A, Alfaro C, Sanmamed MF, Perez\u2010Gracia JL, Penuelas I, Hervas\u2010Stubbs S, Rouzaut A et\u00a0al (2012) The HIF\u20101alpha hypoxia response in tumor\u2010infiltrating T lymphocytes induces functional CD137 (4\u20131BB) for immunotherapy. Cancer Discov 2: 608\u2013623","journal-title":"Cancer Discov"},{"key":"BFEMBJ2021109187_CR64","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.ccell.2017.10.003","volume":"32","author":"A Palazon","year":"2017","unstructured":"Palazon A, Tyrakis PA, Macias D, Velica P, Rundqvist H, Fitzpatrick S, Vojnovic N, Phan AT, Loman N, Hedenfalk I et\u00a0al (2017) An HIF\u20101alpha\/VEGF\u2010A axis in cytotoxic T cells regulates tumor progression. Cancer Cell 32: 669\u2013683","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR65","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1242\/jcs.191395","volume":"129","author":"E Pangou","year":"2016","unstructured":"Pangou E, Befani C, Mylonis I, Samiotaki M, Panayotou G, Simos G, Liakos P (2016) HIF\u20102alpha phosphorylation by CK1delta promotes erythropoietin secretion in liver cancer cells under hypoxia. J Cell Sci 129: 4213\u20134226","journal-title":"J Cell Sci"},{"key":"BFEMBJ2021109187_CR66","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cmet.2016.01.004","volume":"23","author":"SK Ramakrishnan","year":"2016","unstructured":"Ramakrishnan SK, Zhang H, Takahashi S, Centofanti B, Periyasamy S, Weisz K, Chen Z, Uhler MD, Rui L, Gonzalez FJ et\u00a0al (2016) HIF2alpha is an essential molecular brake for postprandial hepatic glucagon response independent of insulin signaling. Cell Metab 23: 505\u2013516","journal-title":"Cell Metab"},{"key":"BFEMBJ2021109187_CR67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aaf4405","volume":"352","author":"EB Rankin","year":"2016","unstructured":"Rankin EB, Giaccia AJ (2016) Hypoxic control of metastasis. Science 352: 175\u2013180","journal-title":"Science"},{"key":"BFEMBJ2021109187_CR70","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1093\/brain\/awq042","volume":"133","author":"S Seidel","year":"2010","unstructured":"Seidel S, Garvalov BK, Wirta V, von Stechow L, Schanzer A, Meletis K, Wolter M, Sommerlad D, Henze AT, Nister M et\u00a0al (2010) A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain 133: 983\u2013995","journal-title":"Brain"},{"key":"BFEMBJ2021109187_CR71","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","volume":"148","author":"GL Semenza","year":"2012","unstructured":"Semenza GL (2012) Hypoxia\u2010inducible factors in physiology and medicine. Cell 148: 399\u2013408","journal-title":"Cell"},{"key":"BFEMBJ2021109187_CR72","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mam.2015.09.004","volume":"47\u201348","author":"GL Semenza","year":"2016","unstructured":"Semenza GL (2016) Dynamic regulation of stem cell specification and maintenance by hypoxia\u2010inducible factors. Mol Aspects Med 47\u201348: 15\u201323","journal-title":"Mol Aspects Med"},{"key":"BFEMBJ2021109187_CR73","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ccell.2017.06.004","volume":"32","author":"SK Shukla","year":"2017","unstructured":"Shukla SK, Purohit V, Mehla K, Gunda V, Chaika NV, Vernucci E, King RJ, Abrego J, Goode GD, Dasgupta A et\u00a0al (2017) MUC1 and HIF\u20101alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell 32: 71\u201387","journal-title":"Cancer Cell"},{"key":"BFEMBJ2021109187_CR74","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139652","volume":"10","author":"S Stalmans","year":"2015","unstructured":"Stalmans S, Bracke N, Wynendaele E, Gevaert B, Peremans K, Burvenich C, Polis I, De Spiegeleer B (2015) Cell\u2010penetrating peptides selectively cross the blood\u2010brain barrier in\u00a0vivo. PLoS One 10: e0139652","journal-title":"PLoS One"},{"key":"BFEMBJ2021109187_CR75","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41586-019-0874-3","volume":"565","author":"S Stegen","year":"2019","unstructured":"Stegen S, Laperre K, Eelen G, Rinaldi G, Fraisl P, Torrekens S, Van Looveren R, Loopmans S, Bultynck G, Vinckier S et\u00a0al (2019) HIF\u20101alpha metabolically controls collagen synthesis and modification in chondrocytes. Nature 565: 511\u2013515","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR76","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1002\/hep.30086","volume":"68","author":"P Sun","year":"2018","unstructured":"Sun P, Lu YX, Cheng D, Zhang K, Zheng J, Liu Y, Wang X, Yuan YF, Tang YD (2018) Monocyte chemoattractant protein\u2010induced protein 1 targets hypoxia\u2010inducible factor 1alpha to protect against hepatic ischemia\/reperfusion injury. Hepatology 68: 2359\u20132375","journal-title":"Hepatology"},{"key":"BFEMBJ2021109187_CR77","doi-asserted-by":"crossref","first-page":"4298","DOI":"10.1093\/emboj\/19.16.4298","volume":"19","author":"K Tanimoto","year":"2000","unstructured":"Tanimoto K, Makino Y, Pereira T, Poellinger L (2000) Mechanism of regulation of the hypoxia\u2010inducible factor\u20101 alpha by the von Hippel\u2010Lindau tumor suppressor protein. EMBO J 19: 4298\u20134309","journal-title":"EMBO J"},{"key":"BFEMBJ2021109187_CR78","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1111\/j.1600-0854.2011.01261.x","volume":"12","author":"C Thorne","year":"2011","unstructured":"Thorne C, Eccles RL, Coulson JM, Urbe S, Clague MJ (2011) Isoform\u2010specific localization of the deubiquitinase USP33 to the Golgi apparatus. Traffic 12: 1563\u20131574","journal-title":"Traffic"},{"key":"BFEMBJ2021109187_CR79","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1101\/gad.11.1.72","volume":"11","author":"H Tian","year":"1997","unstructured":"Tian H, McKnight SL, Russell DW (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 11: 72\u201382","journal-title":"Genes Dev"},{"key":"BFEMBJ2021109187_CR80","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/embr.201337688","volume":"15","author":"A Troilo","year":"2014","unstructured":"Troilo A, Alexander I, Muehl S, Jaramillo D, Knobeloch KP, Krek W (2014) HIF1alpha deubiquitination by USP8 is essential for ciliogenesis in normoxia. EMBO Rep 15: 77\u201385","journal-title":"EMBO Rep"},{"key":"BFEMBJ2021109187_CR81","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.1038\/ncomms6203","volume":"5","author":"T van den Beucken","year":"2014","unstructured":"van den Beucken T, Koch E, Chu K, Rupaimoole R, Prickaerts P, Adriaens M, Voncken JW, Harris AL, Buffa FM, Haider S et\u00a0al (2014) Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nat Commun 5: 5203","journal-title":"Nat Commun"},{"key":"BFEMBJ2021109187_CR82","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/sj.neo.7900192","volume":"3","author":"D Vordermark","year":"2001","unstructured":"Vordermark D, Shibata T, Brown JM (2001) Green fluorescent protein is a suitable reporter of tumor hypoxia despite an oxygen requirement for chromophore formation. Neoplasia 3: 527\u2013534","journal-title":"Neoplasia"},{"key":"BFEMBJ2021109187_CR84","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1038\/nature09421","volume":"467","author":"XZ West","year":"2010","unstructured":"West XZ, Malinin NL, Merkulova AA, Tischenko M, Kerr BA, Borden EC, Podrez EA, Salomon RG, Byzova TV (2010) Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 467: 972\u2013976","journal-title":"Nature"},{"key":"BFEMBJ2021109187_CR85","doi-asserted-by":"crossref","first-page":"13644","DOI":"10.1038\/ncomms13644","volume":"7","author":"HT Wu","year":"2016","unstructured":"Wu HT, Kuo YC, Hung JJ, Huang CH, Chen WY, Chou TY, Chen Y, Chen YJ, Chen YJ, Cheng WC et\u00a0al (2016) K63\u2010polyubiquitinated HAUSP deubiquitinates HIF\u20101alpha and dictates H3K56 acetylation promoting hypoxia\u2010induced tumour progression. Nat Commun 7: 13644","journal-title":"Nat Commun"},{"key":"BFEMBJ2021109187_CR87","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1128\/MCB.01514-06","volume":"27","author":"Q Yan","year":"2007","unstructured":"Yan Q, Bartz S, Mao M, Li L, Kaelin Jr WG (2007) The hypoxia\u2010inducible factor 2alpha N\u2010terminal and C\u2010terminal transactivation domains cooperate to promote renal tumorigenesis in\u00a0vivo. Mol Cell Biol 27: 2092\u20132102","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2021109187_CR88","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1038\/nn.2382","volume":"12","author":"J Yuasa\u2010Kawada","year":"2009","unstructured":"Yuasa\u2010Kawada J, Kinoshita\u2010Kawada M, Wu G, Rao Y, Wu JY (2009) Midline crossing and Slit responsiveness of commissural axons require USP33. Nat Neurosci 12: 1087\u20131089","journal-title":"Nat Neurosci"},{"key":"BFEMBJ2021109187_CR89","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/neuonc\/noaa150","volume":"22","author":"A Zhang","year":"2020","unstructured":"Zhang A, Tao W, Zhai K, Fang X, Huang Z, Yu JS, Solan AE, Rich JN, Zhou W, Bao S (2020) Protein sumoylation with SUMO1 promoted by Pin1 in glioma stem cells augments glioblastoma malignancy. Neuro Oncol 22: 1809\u20131821","journal-title":"Neuro Oncol"},{"key":"BFEMBJ2021109187_CR90","doi-asserted-by":"crossref","first-page":"60519","DOI":"10.18632\/oncotarget.11139","volume":"7","author":"C Zhang","year":"2016","unstructured":"Zhang C, Peng Z, Zhu M, Wang P, Du X, Li X, Liu Y, Jin Y, McNutt MA, Yin Y (2016) USP9X destabilizes pVHL and promotes cell proliferation. Oncotarget 7: 60519\u201360534","journal-title":"Oncotarget"},{"key":"BFEMBJ2021109187_CR91","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.stem.2017.10.002","volume":"21","author":"W Zhou","year":"2017","unstructured":"Zhou W, Chen C, Shi YU, Wu Q, Gimple RC, Fang X, Huang Z, Zhai K, Ke SQ, Ping Y\u2010F et\u00a0al (2017) Targeting glioma stem cell\u2010derived pericytes disrupts the blood\u2010tumor barrier and improves chemotherapeutic efficacy. Cell Stem Cell 21: 591\u2013603","journal-title":"Cell Stem Cell"},{"key":"BFEMBJ2021109187_CR92","doi-asserted-by":"crossref","first-page":"L13","DOI":"10.1530\/ERC-16-0148","volume":"23","author":"Z Zhuang","year":"2016","unstructured":"Zhuang Z, Yang C, Ryska A, Ji Y, Hou Y, Graybill SD, Bullova P, Lubensky IA, Kloppel G, Pacak K (2016) HIF2A gain\u2010of\u2010function mutations detected in duodenal gangliocytic paraganglioma. Endocr Relat Cancer 23: L13\u2013L16","journal-title":"Endocr Relat Cancer"},{"key":"BFEMBJ2021109187_CR93","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12943-019-0987-1","volume":"18","author":"H Zhuo","year":"2019","unstructured":"Zhuo H, Zhao Y, Cheng X, Xu M, Wang L, Lin L, Lyu Z, Hong X, Cai J (2019) Tumor endothelial cell\u2010derived cadherin\u20102 promotes angiogenesis and has prognostic significance for lung adenocarcinoma. Mol Cancer 18: 34","journal-title":"Mol Cancer"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021109187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embj.2021109187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embj.2021109187\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embj.2021109187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021109187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:19:59Z","timestamp":1779308399000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embj.2021109187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":84,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4,4]]}},"alternative-id":["BFEMBJ2021109187"],"URL":"https:\/\/doi.org\/10.15252\/embj.2021109187","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,22]]},"assertion":[{"value":"11 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"EMBJ2021109187"}}