期刊
EMBO JOURNAL
卷 20, 期 23, 页码 6836-6844出版社
NATURE PUBLISHING GROUP
DOI: 10.1093/emboj/20.23.6836
关键词
co-repressor; cytokine; SMRT; STAT; transcription
资金
- NCI NIH HHS [CA21765, P30 CA021765] Funding Source: Medline
- NHLBI NIH HHS [P01 HL53749, P01 HL053749] Funding Source: Medline
- NIDDK NIH HHS [R01 DK042932, R01 DK42932] Funding Source: Medline
Signal transducers and activators of transcription (STATs) play a central role in cytokine signaling. Activating and repressing gene transcription is a dynamic process involving chromatin remodeling by histone acetylases and deacetylases, yet the role of this process in STAT-dependent transcription remains largely unknown. In a search for STAT5-interacting proteins by yeast two-hybrid screening, we identified the nuclear receptor co-repressor SMRT (silencing mediator for retinoic acid receptor and thyroid hormone receptor) as a potential STAT5-binding partner. SMRT binds to both STAT5A and 5B, and strongly repressed STAT5-dependent transcription in vitro. SMRT binds to the N-terminal coiled-coil domain of STAT5 and a mutation within this region previously found to render STAT5 hyperactive in response to cytokines abolished the interaction with SMRT. Overexpression of SMRT suppressed the induction of STAT5 target genes by interleukin-3, whereas the histone deacetylase inhibitor trichostatin A effectively enhanced and prolonged their expression. Together, these findings illuminate the potential role of SMRT in down-regulating STAT5 activity, with a consequent reduction of STAT5 target gene expression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据