{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:53:38Z","timestamp":1777002818579,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A01014"],"award-info":[{"award-number":["GZNL2024A01014"]}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A01016"],"award-info":[{"award-number":["GZNL2024A01016"]}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A01023"],"award-info":[{"award-number":["GZNL2024A01023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin 2 (IL-2) is a cytokine secreted by activated T cells that plays a central role in T cell proliferation and differentiation. In this study, we identified MARCH2, an E3 ubiquitin ligase of the MARCH family, as a negative regulator of IL-2 receptor alpha (IL-2R\u03b1). MARCH2 interacts with IL-2R\u03b1 and catalyzes its K27-linked polyubiquitination and subsequent proteasomal degradation. Site-directed mutagenesis indicates that K267 of IL-2R\u03b1 is targeted by MARCH2 and mutation of this residue impairs MARCH2-mediated polyubiquitination and degradation of IL-2R\u03b1. MARCH2-deficiency promotes IL-2-triggered STAT5 phosphorylation, effector gene expression, and proliferation of activated T cells. Our findings suggest that MARCH2 negatively regulates IL-2 signaling by targeting IL-2R\u03b1 for K27-linked polyubiquitination and proteasomal degradation, uncovering a post-translational mechanism that regulates T cell homeostasis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag045","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:25:18Z","timestamp":1777001118000},"source":"Crossref","is-referenced-by-count":0,"title":["MARCH2 mediates K27-Linked polyubiquitination of IL-2 receptor \u03b1 to negatively regulate T cell proliferation"],"prefix":"10.1093","volume":"215","author":[{"given":"Zhen-Wu","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Hubei Provincial Research Center for Basic Biological Sciences, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University , Wuhan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Hubei Provincial Research Center for Basic Biological Sciences, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University , Wuhan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Ge","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Hubei Provincial Research Center for Basic Biological Sciences, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University , Wuhan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Hubei Provincial Research Center for Basic Biological Sciences, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University , Wuhan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-5198","authenticated-orcid":false,"given":"Shu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Hubei Provincial Research Center for Basic Biological Sciences, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University , 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