Prohibitin is required for transcriptional repression by the WT1-BASP1 complex.
Prohibitin is required for transcriptional repression by the WT1-BASP1 complex.
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Wilms' tumor 1 protein（WT 1）是一种转录调节因子，可以激活或抑制控制细胞生长、凋亡和分化的基因。转录辅抑制因子BASP 1与WT 1相互作用并介导WT 1的转录抑制活性。BASP 1包含在大的复合物中，这表明它与其他因素协同工作。在这里，我们报告的转录抑制物prohibitin是WT 1-BASP 1转录抑制复合物的一部分。Prohibitin与BASP 1相互作用，与BASP 1共定位于细胞核中，并被募集到WT 1靶基因的启动子区，以引发BASP 1依赖性转录抑制。我们证明，抑制素和BASP 1合作招募染色质重塑因子BRG 1到WT 1响应启动子，这导致CBP从WT 1靶基因的启动子区域解离。如BASP 1所示，抑制素可以与磷脂结合。我们证明了PIP 2和HDAC 1向WT 1靶基因的募集也依赖于BASP 1和prohibitin的协同活性。我们的研究结果提供了新的见解，在转录调控中的功能，抑制蛋白，并揭示了BASP 1-抑制蛋白复合物中起着至关重要的作用，在PIP 2依赖的招聘染色质重塑活动的启动子。
The Wilms’ tumor 1 protein (WT1) is a transcriptional regulator that can either activate or repress genes controlling cell growth, apoptosis and differentiation. The transcriptional corepressor BASP1 interacts with WT1 and mediates WT1’s transcriptional repression activity. BASP1 is contained within large complexes, suggesting that it works in concert with other factors. Here we report that the transcriptional repressor prohibitin is part of the WT1-BASP1 transcriptional repression complex. Prohibitin interacts with BASP1, colocalizes with BASP1 in the nucleus, and is recruited to the promoter region of WT1 target genes to elicit BASP1-dependent transcriptional repression. We demonstrate that prohibitin and BASP1 cooperate to recruit the chromatin remodeling factor BRG1 to WT1-responsive promoters and that this results in the dissociation of CBP from the promoter region of WT1 target genes. As seen with BASP1, prohibitin can associate with phospholipids. We demonstrate that the recruitment of PIP2 and HDAC1 to WT1 target genes is also dependent on the concerted activity of BASP1 and prohibitin. Our findings provide new insights into the function of prohibitin in transcriptional regulation and uncover a BASP1-prohibitin complex that plays an essential role in the PIP2-dependent recruitment of chromatin remodeling activities to the promoter.
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DOI：
10.1111/j.1582-4934.2006.tb00404.x
发表时间：
2006-04
影响因子：
5.3
作者：
Mishra S;Murphy LC;Murphy LJ
通讯作者：
Murphy LJ
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
8
作者：
Choi, D.;Lee, S-J;Kang, S.
通讯作者：
Kang, S.
DOI：
10.1042/bj20101734
发表时间：
2011-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Goodfellow SJ;Rebello MR;Toska E;Zeef LA;Rudd SG;Medler KF;Roberts SG
通讯作者：
Roberts SG
影响因子：
10.5
作者：
Han, Bong-Kwan;Emr, Scott D.
通讯作者：
Emr, Scott D.