...
首页> 外文期刊>Molecular and Cellular Biology >Phosphorylation-Dependent Regulation of Cyclin D1 and Cyclin A Gene Transcription by TFIID Subunits TAF1 and TAF7
【24h】

Phosphorylation-Dependent Regulation of Cyclin D1 and Cyclin A Gene Transcription by TFIID Subunits TAF1 and TAF7

机译:TFIID亚基TAF1和TAF7的细胞周期蛋白D1和细胞周期蛋白A基因转录的磷酸化依赖性调控

获取原文
           

摘要

The largest transcription factor IID (TFIID) subunit, TBP-associated factor 1 (TAF1), possesses protein kinase and histone acetyltransferase (HAT) activities. Both enzymatic activities are essential for transcription from a subset of genes and G1 progression in mammalian cells. TAF7, another TFIID subunit, binds TAF1 and inhibits TAF1 HAT activity. Here we present data demonstrating that disruption of the TAF1/TAF7 interaction within TFIID by protein phosphorylation leads to activation of TAF1 HAT activity and stimulation of cyclin D1 and cyclin A gene transcription. Overexpression and small interfering RNA knockdown experiments confirmed that TAF7 functions as a transcriptional repressor at these promoters. Release of TAF7 from TFIID by TAF1 phosphorylation of TAF7 increased TAF1 HAT activity and elevated histone H3 acetylation levels at the cyclin D1 and cyclin A promoters. Serine-264 of TAF7 was identified as a substrate for TAF1 kinase activity. Using TAF7 S264A and S264D phosphomutants, we determined that the phosphorylation state of TAF7 at S264 influences the levels of cyclin D1 and cyclin A gene transcription and promoter histone H3 acetylation. Our studies have uncovered a novel function for the TFIID subunit TAF7 as a phosphorylation-dependent regulator of TAF1-catalyzed histone H3 acetylation at the cyclin D1 and cyclin A promoters.
机译:最大的转录因子IID(TFIID)亚基,TBP相关因子1(TAF1),具有蛋白激酶和组蛋白乙酰转移酶(HAT)活性。这两种酶活性对于从哺乳动物细胞中的一个基因子集转录和G 1 进程都是必不可少的。 TAF7是另一个TFIID亚基,与TAF1结合并抑制TAF1 HAT活性。在这里,我们提供的数据表明,通过蛋白质磷酸化破坏TFIID内的TAF1 / TAF7相互作用会导致TAF1 HAT活性的激活以及细胞周期蛋白D1和细胞周期蛋白A基因转录的刺激。过表达和小干扰RNA敲低实验证实,TAF7在这些启动子上起转录阻遏物的作用。 TAF7的TAF1磷酸化使TAF7从TFIID释放,增加了TAF1 HAT活性,并提高了细胞周期蛋白D1和细胞周期蛋白A启动子的组蛋白H3乙酰化水平。 TAF7的丝氨酸264被确定为TAF1激酶活性的底物。使用TAF7 S264A和S264D磷酸突变体,我们确定了TAF7在S264的磷酸化状态影响细胞周期蛋白D1和细胞周期蛋白A基因的转录水平以及启动子组蛋白H3乙酰化。我们的研究发现了TFIID亚基TAF7作为细胞周期蛋白D1和细胞周期蛋白A启动子上TAF1催化的组蛋白H3乙酰化的依赖磷酸化的调节剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号