Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 황은숙 | * |
dc.date.accessioned | 2016-08-28T10:08:02Z | - |
dc.date.available | 2016-08-28T10:08:02Z | - |
dc.date.issued | 2013 | * |
dc.identifier.issn | 0022-1767 | * |
dc.identifier.other | OAK-10119 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/223755 | - |
dc.description.abstract | AT-box-containing protein expressed in T cells (T-bet) is a key transcription factor involved in the regulation of Th cell differentiation. Although T-bet-deficient CD4+ T cells fail to produce IFN-γ and typically differentiate into Th2 cells in vitro, ectopic overexpression of T-bet elevates IFN-γ and suppresses production of IL-2 and Th2 cytokines through different mechanisms. Despite the importance of the T-bet protein level, the regulatory mechanisms that control T-bet protein stability are largely unknown. In this study, we found that T-bet underwent proteasomal degradation via ubiquitination at Lys-313. Despite its robust accumulation following lysine mutation, T-betK313R failed to increase IFN-γ production because of diminished DNA binding activity, as demonstrated in the crystal structure of T-bet-DNA complex. Strikingly, T-betK313R entirely lost the ability to suppress IL-2 production and Th2 cell development; this was due to loss of its interaction with NFAT1. We further identified that the T-bet K313R reduced the phosphorylation of T-bet at Thr-302, and that threonine phosphorylation was essential for T-bet interaction with NFAT1 and suppression of NFAT1 activity. Retroviral transduction of T-betT302A into T-bet-deficient cells restored IFN-γ levels compared with those induced by wild-type T-bet, but this mutant failed to inhibit IL-2 and Th2 cytokine production. Collectively, these data show that Lys-313 in the T-box domain is essential for controlling T-bet protein stability via ubiquitin-dependent degradation, T-bet binding to the IFN-γ promoter, and for the interaction with and suppression of NFAT1. Thus, multiple posttranslational modifications of T-bet are involved in fine-tuning cytokine production during Th cell development. Copyright © 2013 by The American Association of Immunologists, Inc. | * |
dc.language | English | * |
dc.title | Lysine 313 of T-box is crucial for modulation of protein stability, DNA binding, and threonine phosphorylation of T-bet | * |
dc.type | Article | * |
dc.relation.issue | 11 | * |
dc.relation.volume | 190 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 5764 | * |
dc.relation.lastpage | 5770 | * |
dc.relation.journaltitle | Journal of Immunology | * |
dc.identifier.doi | 10.4049/jimmunol.1203403 | * |
dc.identifier.wosid | WOS:000319205900047 | * |
dc.identifier.scopusid | 2-s2.0-84878073297 | * |
dc.author.google | Jang E.J. | * |
dc.author.google | Park H.R. | * |
dc.author.google | Hong J.-H. | * |
dc.author.google | Hwang E.S. | * |
dc.contributor.scopusid | 황은숙(8688011100) | * |
dc.date.modifydate | 20240123102458 | * |