The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6
The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6
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DOI：
10.1074/jbc.m404428200
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发表时间：
2004-07-23
影响因子：
4.8
通讯作者：
Rothman, PB
中科院分区：
文献类型：
--
作者：
Arimura, A;van Peer, M;Rothman, PB
信号转导子和转录激活子6（STAT 6）的转录激活不仅需要与辅激活子如p300和cAMP反应元件结合蛋白结合蛋白（CBP）直接相互作用，而且需要与核辅激活子1（p160/类固醇受体辅激活子家族的成员）直接相互作用。在p160/类固醇受体辅激活因子中，使用Gene-hip分析显示，只有p/CIP（核辅激活因子3）通过STAT-6依赖性机制在B细胞中被白细胞介素（IL）-4上调。在这项研究中，我们研究了p/CIP在STAT 6转录激活中的功能。我们发现p/CIP通过p300与STAT 6间接相互作用，并且p/CIP的CBP相互作用结构域（p/CIP 947 -1084）的过表达通过阻断p/CIP与p300的结合来阻止p/CIP与STAT 6的相互作用。而p/CIP 947 -1084的表达导致STAT 6介导的反式激活的显著降低，野生型p/CIP的过表达导致其显著增强。此外，p/CIP 947 -1084显著降低用IL-4刺激的B细胞上的CD 23表达，而野生型p/CIP的过表达增强了它。染色质免疫沉淀表明IL-4增强了p/CIP的相互作用。在B细胞中用鼠免疫球蛋白重链种系启动子进行CIP。这些结果表明p/CIP通过形成STAT 6、p300/ CBP和p/CIP复合物正调控STAT 6转录激活。
Transcriptional activation by signal transducer and activator of transcription 6 (STAT6) has been shown to require the direct interaction not only with co-activators such as p300 and cAMP-responsive element-binding protein-binding protein (CBP) but also with nuclear coactivator 1, a member of the p160/steroid receptor coactivator family. Among the p160/steroid receptor coactivators, only p/CIP ( nuclear co-activator 3) has been shown to be up-regulated by interleukin (IL)-4 in B cells through a STAT-6-dependent mechanism using Gene-hip analysis. In this study, we have investigated the function of p/CIP in the transcriptional activation by STAT6. We found that p/CIP indirectly interacted with STAT6 via p300, and overexpression of the CBP-interacting domain of p/CIP (p/CIP947-1084) prevented the interaction of p/CIP with STAT6 by blocking the binding of p/CIP to p300. Whereas expression of p/CIP947-1084 resulted in a marked reduction of STAT6-mediated transactivation, overexpression of wild type p/CIP resulted in significant enhancement of it. In addition, p/CIP947-1084 markedly reduced CD23 expression on B cells stimulated with IL-4, whereas overexpression of wild type p/CIP enhanced it. Chromatin immunoprecipitations demonstrate that IL-4 increases the interaction of p/CIP with the murine immunoglobulin heavy chain germ line epsilon promoter in B cells. These results suggest that p/CIP positively regulates STAT6 transcriptional activation through formation of a STAT6, p300/ CBP, and p/CIP complex.