Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA
Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA
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DOI：
10.1016/s1097-2765(03)00388-5
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发表时间：
2003-10-01
期刊：
影响因子：
16
通讯作者：
Zhou, Q
中科院分区：
文献类型：
--
作者：
Yik, JHN;Chen, RC;Zhou, Q
正转录延伸因子B（P-TEF B）由CDK 9和细胞周期蛋白T组成，通过磷酸化RNA聚合酶II刺激转录。当与丰富的7SK snRNA结合时，它变得失活。在这里，我们表明单独的7SK结合不足以抑制P-TEFb。P-TEFb被HEXIM 1蛋白抑制，该过程特别需要7SK来介导HEXIM 1：P-TEFb相互作用。这使得HEXIM 1能够在体内和体外抑制转录。P-TEFb在经历应激反应的细胞中从HEXIM 1和7SK解离，增加了应激诱导转录的活性P-TEFb的水平。P-TEFb是主要的HEXIM 1相关蛋白因子，因此可能是HEXIM 1和7SK协调抑制的主要靶标。由于HEXIM 1表达在用双乙酰胺（一种有效的细胞分化诱导剂）处理的细胞中被诱导，因此通过HEXIM 1/7SK靶向一般转录因子P-TEFb可能有助于细胞生长和分化的全面控制。
The positive transcriptional elongation factor b (P-TEFb), consisting of CDK9 and cyclin T, stimulates transcription by phosphorylating RNA polymerase II. It becomes inactivated when associated with the abundant 7SK snRNA. Here, we show that the 7SK binding alone was not sufficient to inhibit P-TEFb. P-TEFb was inhibited by the HEXIM1 protein in a process that specifically required 7SK for mediating the HEXIM1:P-TEFb interaction. This allowed HEXIM1 to inhibit transcription both in vivo and in vitro. P-TEFb dissociated from HEXIM1 and 7SK in cells undergoing stress response, increasing the level of active P-TEFb for stress-induced transcription. P-TEFb was the predominant HEXIM1-associated protein factor, and thus likely to be the principal target of inhibition coordinated by HEXIM1 and 7SK. Since HEXIM1 expression is induced in cells treated with hexamethylene bisacetamide, a potent inducer of cell differentiation, targeting the general transcription factor P-TEFb by HEXIM1/7SK may contribute to the global control of cell growth and differentiation.