{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:28:34Z","timestamp":1782188914353,"version":"3.54.5"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is not clear why the development of protective Th2 cells is poor in type 1 diabetes (T1D). c-Maf transactivates the IL-4 gene promoting Th2 cell development; therefore, abnormalities in c-Maf may contribute to reduced IL-4 production by CD4 cells from nonobese diabetic (NOD) mice. In this study we demonstrate that despite normal expression, c-Maf binds poorly to the IL-4 promoter (IL-4p) in NOD CD4 cells. Immunoblotting demonstrates that c-Maf can be modified at lysine 33 by SUMO-1 (small ubiquitin-like modifier 1). Sumoylation is facilitated by direct interaction with the E2-conjugating enzyme Ubc9 and increases following T cell stimulation. In transfected cells, sumoylation decreases c-Maf transactivation of IL-4p-driven luciferase reporter activity, reduces c-Maf binding to the IL-4p in chromatin immunoprecipitation assays, and enhances c-Maf localization into promyelocytic leukemia nuclear bodies. Sumoylation of c-Maf is increased in NOD CD4 cells as compared with CD4 cells from diabetes-resistant B10.D2 mice, suggesting that increased c-Maf sumoylation contributes to immune deviation in T1D by reducing c-Maf access to and transactivation of the IL-4 gene.<\/jats:p>","DOI":"10.4049\/jimmunol.0803671","type":"journal-article","created":{"date-parts":[[2009,6,24]],"date-time":"2009-06-24T22:00:49Z","timestamp":1245880849000},"page":"1110-1119","source":"Crossref","is-referenced-by-count":21,"title":["SUMO Conjugation Contributes to Immune Deviation in Nonobese Diabetic Mice by Suppressing c-Maf Transactivation of\n                    <i>IL-4<\/i>"],"prefix":"10.1093","volume":"183","author":[{"given":"Jianmei W","family":"Leavenworth","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-yuan","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E","family":"Pauza","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Immunology, and Cell Biology"},{"name":"Department of Internal Medicine, Southern Illinois University School of Medicine , Springfield, IL 62702"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,15]]},"reference":[{"key":"2026012811300019000_R1","first-page":"1185","article-title":"T helper cell subsets in insulin-dependent diabetes.","volume-title":"Science","year":"1995"},{"key":"2026012811300019000_R2","first-page":"2414","article-title":"IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice.","volume-title":"J. 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A role in transcriptional regulation.","volume-title":"EMBO Rep.","year":"2003"},{"key":"2026012811300019000_R13","first-page":"355","article-title":"Protein modification by SUMO.","volume-title":"Annu. Rev. Biochem.","year":"2004"},{"key":"2026012811300019000_R14","first-page":"1998","article-title":"SUMO: a regulator of gene expression and genome integrity.","volume-title":"Oncogene","year":"2004"},{"key":"2026012811300019000_R15","first-page":"2298","article-title":"Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by quantitative proteomics.","volume-title":"Mol. Cell. Proteomics","year":"2006"},{"key":"2026012811300019000_R16","first-page":"27233","article-title":"A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.","volume-title":"J. Biol. 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