{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:33:33Z","timestamp":1790692413595,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T00:00:00Z","timestamp":1546905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protein-templated fragment ligations have been established as a powerful method for the assembly and detection of optimized protein ligands. Initially developed for reversible ligations, the method has been expanded to irreversible reactions enabling the formation of super-additive fragment combinations. Here, protein-induced Mannich ligations are discovered as a biocatalytic reaction furnishing inhibitors of the transcription factor STAT5. STAT5 protein catalyzes multicomponent reactions of a phosphate mimetic, formaldehyde, and 1<jats:italic>H<\/jats:italic>-tetrazoles yielding protein ligands with greatly increased binding affinity and ligand efficiency. Reactions are induced under physiological conditions selectively by native STAT5 but not by other proteins. Formation of ligation products and (auto-)inhibition of the reaction are quantified and the mechanism is investigated. Inhibitors assembled by STAT5 block specifically the phosphorylation of this protein in a cellular model of acute myeloid leukemia (AML), DNA-binding of STAT5 dimers, expression of downstream targets of the transcription factor, and the proliferation of cancer cells in mice.<\/jats:p>","DOI":"10.1038\/s41467-018-07923-2","type":"journal-article","created":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T11:42:56Z","timestamp":1546429376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The transcription factor STAT5 catalyzes Mannich ligation reactions yielding inhibitors of leukemic cell proliferation"],"prefix":"10.1038","volume":"10","author":[{"given":"Ee Lin","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Nawrotzky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Arkona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boo Geun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Beligny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lisurek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Carstanjen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-3165","authenticated-orcid":false,"given":"J\u00f6rg","family":"Rademann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"7923_CR1","doi-asserted-by":"publisher","first-page":"7358","DOI":"10.1002\/anie.201610372","volume":"56","author":"M Jaegle","year":"2017","unstructured":"Jaegle, M. et al. Protein-templated fragment ligations - from molecular recognition to drug discovery. Angew. Chem. Int. Ed. 56, 7358\u20137378 (2017).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR2","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1039\/C3CS60336A","volume":"43","author":"A Herrmann","year":"2014","unstructured":"Herrmann, A. Dynamic combinatorial\/covalent chemistry: a tool to read, generate and modulate the bioactivity of compounds and compound mixtures. Chem. Soc. Rev. 43, 1899\u20131933 (2014).","journal-title":"Chem. Soc. Rev."},{"key":"7923_CR3","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1039\/C4CS00493K","volume":"44","author":"M Mondal","year":"2015","unstructured":"Mondal, M. & Hirsch, A. K. H. Dynamic combinatorial chemistry: a tool to facilitate the identification of inhibitors for protein targets. Chem. Soc. Rev. 44, 2455\u20132488 (2015).","journal-title":"Chem. Soc. Rev."},{"key":"7923_CR4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/nrd704","volume":"1","author":"O Ramstr\u00f6m","year":"2002","unstructured":"Ramstr\u00f6m, O. & Lehn, J.-M. Drug discovery by dynamic combinatorial libraries. Nat. Rev. Drug. Discov. 1, 26\u201336 (2002).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"7923_CR5","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1002\/cbic.201100414","volume":"12","author":"MF Schmidt","year":"2011","unstructured":"Schmidt, M. F., Groves, M. R. & Rademann, J. Dynamic substrate enhancement for the identification of specific, second-site-binding fragments targeting a set of protein tyrosine phosphatases. Chembiochem 12, 2640\u20132646 (2011).","journal-title":"Chembiochem"},{"key":"7923_CR6","doi-asserted-by":"crossref","unstructured":"Jaegle, M., Nawrotzky, E., Wong, E. L., Arkona, C. & Rademann, J. in Fragment-based Drug Discovery Lessons and Outlook (eds Erlanson, D. A. & Jahnke, W.) 293\u2013326 (Wiley-VCH Verlag GmbH & Co. KGaA, 2016).","DOI":"10.1002\/9783527683604.ch13"},{"key":"7923_CR7","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.tibtech.2009.06.001","volume":"27","author":"MF Schmidt","year":"2009","unstructured":"Schmidt, M. F. & Rademann, J. Dynamic template-assisted strategies in fragment-based drug discovery. Trends Biotechnol. 27, 512\u2013521 (2009).","journal-title":"Trends Biotechnol."},{"key":"7923_CR8","doi-asserted-by":"publisher","first-page":"3275","DOI":"10.1002\/anie.200704594","volume":"47","author":"MF Schmidt","year":"2008","unstructured":"Schmidt, M. F. et al. Sensitized detection of inhibitory fragments and iterative development of non-peptidic protease inhibitors by dynamic ligation screening. Angew. Chem. Int. Ed. 47, 3275\u20133278 (2008).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6170","volume":"5","author":"E Burda","year":"2014","unstructured":"Burda, E. & Rademann, J. Catalytic activation of pre-substrates via dynamic fragment assembly on protein templates. Nat. Commun. 5, 5170 (2014).","journal-title":"Nat. Commun."},{"key":"7923_CR10","doi-asserted-by":"publisher","first-page":"6346","DOI":"10.1002\/anie.200901647","volume":"48","author":"MF Schmidt","year":"2009","unstructured":"Schmidt, M. F., El-Dahshan, A., Keller, S. & Rademann, J. Selective identification of cooperatively binding fragments in a high-throughput ligation assay enables development of a picomolar caspase-3 inhibitor. Angew. Chem. Int. Ed. 48, 6346\u20136349 (2009).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR11","doi-asserted-by":"publisher","first-page":"9367","DOI":"10.1073\/pnas.97.17.9367","volume":"97","author":"DA Erlanson","year":"2000","unstructured":"Erlanson, D. A. et al. Site-directed ligand discovery. Proc. Natl. Acad. Sci. USA 97, 9367\u20139372 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"7923_CR12","doi-asserted-by":"publisher","first-page":"6817","DOI":"10.1002\/anie.201002205","volume":"49","author":"T Suzuki","year":"2010","unstructured":"Suzuki, T. et al. An unexpected example of protein-templated click chemistry. Angew. Chem. Int. Ed. 49, 6817\u20136820 (2010).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR13","doi-asserted-by":"publisher","first-page":"13820","DOI":"10.1021\/ja802683u","volume":"130","author":"X Hu","year":"2008","unstructured":"Hu, X., Sun, J., Wang, H.-G. & Manetsch, R. Bcl-XL-templated assembly of its own protein\u2212 protein interaction modulator from fragments decorated with thio acids and sulfonyl azides. J. Am. Chem. Soc. 130, 13820\u201313821 (2008).","journal-title":"J. Am. Chem. Soc."},{"key":"7923_CR14","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1021\/cb200085q","volume":"6","author":"SS Kulkarni","year":"2011","unstructured":"Kulkarni, S. S., Hu, X., Doi, K., Wang, H.-G. & Manetsch, R. Screening of protein\u2013protein interaction modulators via sulfo-click kinetic target-guided synthesis. ACS Chem. Biol. 6, 724\u2013732 (2011).","journal-title":"ACS Chem. Biol."},{"key":"7923_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12761","volume":"7","author":"D Becker","year":"2016","unstructured":"Becker, D. et al. Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments. Nat. Commun. 7, 12761 (2016).","journal-title":"Nat. Commun."},{"key":"7923_CR16","doi-asserted-by":"publisher","first-page":"3718","DOI":"10.1002\/anie.201611547","volume":"56","author":"M Jaegle","year":"2017","unstructured":"Jaegle, M., Steinmetzer, T. & Rademann, J. Protein-templated formation of an inhibitor of the blood coagulation Factor Xa through a background-free amidation reaction. Angew. Chem. Int. Ed. 56, 3718\u20133722 (2017).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.4161\/jkst.20006","volume":"1","author":"M Bar-Natan","year":"2012","unstructured":"Bar-Natan, M., Nelson, E. A., Xiang, M. & Frank, D. A. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAK-STAT 1, 55\u201364 (2012).","journal-title":"JAK-STAT"},{"key":"7923_CR18","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1039\/C1MD00175B","volume":"3","author":"AA Cumaraswamy","year":"2012","unstructured":"Cumaraswamy, A. A., Todic, A., Resetca, D., Minden, M. D. & Gunning, P. T. Inhibitors of Stat5 protein signalling. MedChemComm 3, 22\u201327 (2012).","journal-title":"MedChemComm"},{"key":"7923_CR19","doi-asserted-by":"crossref","unstructured":"Gianti, E. & Zauhar, R. An SH2 domain model of STAT5 in complex with phospho-peptides define \u201cSTAT5-binding signatures\u201d. J. Comput. Aided Mol. Des. 25, 1\u201320 (2015).","DOI":"10.1007\/s10822-015-9835-6"},{"key":"7923_CR20","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1158\/1535-7163.MCT-13-0341","volume":"13","author":"S Liu","year":"2014","unstructured":"Liu, S. et al. Targeting STAT5 in hematological malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2. Mol. Cancer Ther. 13, 1194\u20131205 (2014).","journal-title":"Mol. Cancer Ther."},{"key":"7923_CR21","doi-asserted-by":"publisher","first-page":"9441","DOI":"10.1002\/anie.201201475","volume":"51","author":"A Horatscheck","year":"2012","unstructured":"Horatscheck, A. et al. Benzoylphosphonate-based photoactive phosphopeptide mimetics for modulation of protein tyrosine phosphatases and highly specific labeling of SH2 domains. Angew. Chem. Int. Ed. 51, 9441\u20139447 (2012).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR22","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1016\/j.chembiol.2006.09.018","volume":"13","author":"J Schust","year":"2006","unstructured":"Schust, J., Sperl, B., Hollis, A., Mayer, T. U. & Berg, T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem. Biol. 13, 1235\u20131242 (2006).","journal-title":"Chem. Biol."},{"key":"7923_CR23","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1021\/ml500165r","volume":"5","author":"AA Cumaraswamy","year":"2014","unstructured":"Cumaraswamy, A. A. et al. Nanomolar-potency small molecule inhibitor of STAT5 protein. ACS Med. Chem. Lett. 5, 1202\u20131206 (2014).","journal-title":"ACS Med. Chem. Lett."},{"key":"7923_CR24","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1002\/anie.201410672","volume":"54","author":"N Elumalai","year":"2015","unstructured":"Elumalai, N., Berg, A., Natarajan, K., Scharow, A. & Berg, T. Nanomolar inhibitors of the transcription factor STAT5b with high selectivity over STAT5a. Angew. Chem. Int. Ed. 54, 4758\u20134763 (2015).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR25","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1021\/jm200720n","volume":"55","author":"BDG Page","year":"2012","unstructured":"Page, B. D. G. et al. Small molecule STAT5-SH2 domain inhibitors exhibit potent antileukemia activity. J. Med. Chem. 55, 1047\u20131055 (2012).","journal-title":"J. Med. Chem."},{"key":"7923_CR26","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s11030-009-9187-z","volume":"14","author":"M Lisurek","year":"2010","unstructured":"Lisurek, M. et al. Design of chemical libraries with potentially bioactive molecules applying a maximum common substructure concept. Mol. Divers. 14, 401\u2013408 (2010).","journal-title":"Mol. Divers."},{"key":"7923_CR27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nrd4163","volume":"13","author":"AL Hopkins","year":"2014","unstructured":"Hopkins, A. L., Keseru, G. M., Leeson, P. D., Rees, D. C. & Reynolds, C. H. The role of ligand efficiency metrics in drug discovery. Nat. Rev. Drug. Discov. 13, 105\u2013121 (2014).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"7923_CR28","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/978-1-61779-337-0_7","volume":"795","author":"O Fedorov","year":"2012","unstructured":"Fedorov, O., Niesen, F. H. & Knapp, S. Kinase inhibitor selectivity profiling using differential scanning fluorimetry. Methods Mol. Biol. 795, 109\u2013118 (2012).","journal-title":"Methods Mol. Biol."},{"key":"7923_CR29","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1038\/nprot.2007.321","volume":"2","author":"FH Niesen","year":"2007","unstructured":"Niesen, F. H., Berglund, H. & Vedadi, M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2, 2212\u20132221 (2007).","journal-title":"Nat. Protoc."},{"key":"7923_CR30","doi-asserted-by":"publisher","first-page":"40782","DOI":"10.1074\/jbc.M507682200","volume":"280","author":"D Neculai","year":"2005","unstructured":"Neculai, D. et al. Structure of the unphosphorylated STAT5a dimer. J. Biol. Chem. 280, 40782\u201340787 (2005).","journal-title":"J. Biol. Chem."},{"key":"7923_CR31","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.cell.2008.11.038","volume":"136","author":"AJ Barr","year":"2009","unstructured":"Barr, A. J. et al. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell 136, 352\u2013363 (2009).","journal-title":"Cell"},{"key":"7923_CR32","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1002\/anie.200603420","volume":"46","author":"AK Hirsch","year":"2007","unstructured":"Hirsch, A. K., Fischer, F. R. & Diederich, F. Phosphate recognition in structural biology. Angew. Chem. Int. Ed. 46, 338\u2013352 (2007).","journal-title":"Angew. Chem. Int. Ed."},{"key":"7923_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00920-3","volume":"7","author":"N Elumalai","year":"2017","unstructured":"Elumalai, N. et al. Rational development of Stafib-2: a selective, nanomolar inhibitor of the transcription factor STAT5b. Sci. Rep. 7, 819 (2017).","journal-title":"Sci. Rep."},{"key":"7923_CR34","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/s41375-017-0005-9","volume":"32","author":"B Wingelhofer","year":"2018","unstructured":"Wingelhofer, B. et al. Pharmacologic inhibition of STAT5 in acute myeloid leukemia. Leukemia 32, 1135\u20131146 (2018).","journal-title":"Leukemia"},{"key":"7923_CR35","doi-asserted-by":"crossref","unstructured":"Almqvist, H. et al. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil. Nat. Commun. 7, 11040 (2016).","DOI":"10.1038\/ncomms11040"},{"key":"7923_CR36","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.1233606","volume":"341","author":"DM Molina","year":"2013","unstructured":"Molina, D. M. et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. Science 341, 84\u201387 (2013).","journal-title":"Science"},{"key":"7923_CR37","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1182\/blood.V96.12.3907","volume":"96","author":"M Mizuki","year":"2000","unstructured":"Mizuki, M. et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood 96, 3907\u20133914 (2000).","journal-title":"Blood"},{"key":"7923_CR38","doi-asserted-by":"publisher","first-page":"5089","DOI":"10.1182\/blood-2010-04-261867","volume":"116","author":"T Kindler","year":"2010","unstructured":"Kindler, T., Lipka, D. B. & Fischer, T. FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 116, 5089\u20135102 (2010).","journal-title":"Blood"},{"key":"7923_CR39","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.1021\/jm2000882","volume":"54","author":"PK Mandal","year":"2011","unstructured":"Mandal, P. K. et al. Potent and selective phosphopeptide mimetic prodrugs targeted to the Src Homology 2 (SH2) domain of signal transducer and activator of transcription 3. J. Med. Chem. 54, 3549\u20133563 (2011).","journal-title":"J. Med. Chem."},{"key":"7923_CR40","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1038\/nprot.2014.138","volume":"9","author":"R Jafari","year":"2014","unstructured":"Jafari, R. et al. The cellular thermal shift assay for evaluating drug target interactions in cells. Nat. Protoc. 9, 2100\u20132122 (2014).","journal-title":"Nat. Protoc."},{"key":"7923_CR41","first-page":"17","volume":"15","author":"D Fabbro","year":"2000","unstructured":"Fabbro, D. et al. PKC412-a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 15, 17\u201328 (2000).","journal-title":"Anticancer Drug Des."},{"key":"7923_CR42","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S1535-6108(02)00069-7","volume":"1","author":"E Weisberg","year":"2002","unstructured":"Weisberg, E. et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 1, 433\u2013443 (2002).","journal-title":"Cancer Cell"},{"key":"7923_CR43","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou, T. C. Drug combination studies and their synergy quantification using the Chou\u2013Talalay method. Cancer Res. 70, 440\u2013446 (2010).","journal-title":"Cancer Res."},{"key":"7923_CR44","doi-asserted-by":"crossref","unstructured":"Croucher, D. C. et al. The potent STAT3\/5 Inhibitor, BP-1-102 demonstrates significant anti-tumor activity against Waldenstr\u00f6m Macroglobulinemia. Am. Soc. Hematol. 118, 5101-5101 (2011).","DOI":"10.1182\/blood.V118.21.5101.5101"},{"key":"7923_CR45","doi-asserted-by":"crossref","unstructured":"Lim, J. S. J. et al. Extended cohort study of OPB51602, a novel inhibitor of STAT3\/5 activation, in non-small cell lung carcinoma. Am. J. Clin. Oncol. 15, 8028\u20138028 (2014).","DOI":"10.1200\/jco.2014.32.15_suppl.8028"},{"key":"7923_CR46","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nature23481","volume":"548","author":"G Burgos-Barragan","year":"2017","unstructured":"Burgos-Barragan, G. et al. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 548, 549 (2017).","journal-title":"Nature"},{"key":"7923_CR47","doi-asserted-by":"publisher","first-page":"10886","DOI":"10.1021\/jacs.5b05340","volume":"137","author":"TF Brewer","year":"2015","unstructured":"Brewer, T. F. & Chang, C. J. An aza-cope reactivity-based fluorescent probe for imaging formaldehyde in living cells. J. Am. Chem. Soc. 137, 10886\u201310889 (2015).","journal-title":"J. Am. Chem. Soc."},{"key":"7923_CR48","doi-asserted-by":"publisher","first-page":"e81504","DOI":"10.1371\/journal.pone.0081504","volume":"8","author":"SN Krishna","year":"2013","unstructured":"Krishna, S. N. et al. A fluorescence-based thermal shift assay identifies inhibitors of mitogen activated protein kinase kinase 4. PLoS. ONE 8, e81504 (2013).","journal-title":"PLoS. ONE"},{"key":"7923_CR49","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.bbamcr.2009.01.017","volume":"1793","author":"YH Qian","year":"2009","unstructured":"Qian, Y.-H., Xiao, Q., Chen, H. & Xu, J. Dexamethasone inhibits camptothecin-induced apoptosis in C6-glioma via activation of Stat5\/Bcl-xL pathway. Biochim. Biophys. Acta 1793, 764\u2013771 (2009).","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07923-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07923-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07923-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T18:38:12Z","timestamp":1671215892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07923-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,8]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["7923"],"URL":"https:\/\/doi.org\/10.1038\/s41467-018-07923-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,8]]},"assertion":[{"value":"17 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"66"}}