SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription
SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription
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DOI：
10.1074/jbc.m111987200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Choe, J
中科院分区：
文献类型：
--
作者：
Lee, D;Kim, JW;Choe, J
SWI/SNF复合体是几种基因转录所必需的，并且已被证明以atp依赖的方式改变核小体结构。肿瘤抑制蛋白p53显示出生长和转化抑制功能，在各种癌症中检测到的突变p53蛋白中经常失去这种功能。利用遗传和生化方法，我们发现人类SWI/SNF复合物的几个亚基在体内和体外与肿瘤抑制蛋白p53结合。hSNF5和BRG-1的过表达刺激了p53的转激活功能，hSNF5和BRG-1的显性形式抑制了p53依赖的转录。染色质免疫沉淀实验表明，hSNF5和BRG-1在体内被募集到p53依赖的启动子上。hSNF5或BRG-1显性阴性形式的过表达可抑制p53介导的细胞生长抑制和凋亡。p53和SWI/SNF复合物之间的分子联系表明(i) SWI/SNF复合物是p53驱动的转录激活所必需的，（ii） SWI/SNF复合物在p53介导的细胞周期控制中起重要作用。
The SWI/SNF complex is required for the transcription of several genes and has been shown to alter nucleosome structure in an ATP-dependent manner. The tumor suppressor protein p53 displays growth and transformation suppression functions that are frequently lost in mutant p53 proteins detected in various cancers. Using genetic and biochemical approaches, we show that several subunits of the human SWI/SNF complex bind to the tumor suppressor protein p53 in vivo and in vitro. The transactivation function of p53 is stimulated by overexpression of hSNF5 and BRG-1 and dominant forms of hSNF5 and BRG-1 repress p53-dependent transcription. Chromatin immunoprecipitation assay shows that hSNF5 and BRG-1 are recruited to a p53-dependent promoter in vivo. Overexpression of dominant negative forms of either hSNF5 or BRG-1 inhibited p53-mediated cell growth suppression and apoptosis. Molecular connection between p53 and the SWI/SNF complex implicates that (i) the SWI/SNF complex is necessary for p53-driven transcriptional activation, and (ii) the SWI/SNF complex plays an important role in p53-mediated cell cycle control.