Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells
Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells
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DOI：
10.1038/emboj.2009.99
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发表时间：
2009-05-20
期刊：
影响因子：
11.4
通讯作者：
Ott, Melanie
中科院分区：
文献类型：
--
作者：
Cho, Sungyoo;Schroeder, Sebastian;Ott, Melanie
RNA聚合酶II复合物的延伸能力严重依赖于正转录延伸因子B（P-TEF B）。P-TEFb在细胞中以两种形式存在，一种是由细胞周期蛋白T1和CDK 9组成的活性形式，另一种是由Hexim 1和7SK snRNA隔离的非活性形式。在这里，我们报告说，分区的活性和非活性P-TEFb的调节乙酰化的细胞周期蛋白T1。细胞周期蛋白T1乙酰化触发Hexim 1和7SK snRNA从细胞周期蛋白T1/CDK 9解离并激活P-TEFb的转录活性。这种激活在含有不能再乙酰化的细胞周期蛋白T1的P-TEFb复合物中丧失。乙酰化缺陷的细胞周期蛋白T1突变体主要抑制NF-κ B介导的白细胞介素-8启动子的激活，但继续与HIV达特蛋白正常协同作用，以反式激活HIV长末端重复序列。这些发现支持了这样的模型，即细胞周期蛋白T1的乙酰化作为生理开关，将P-TEFb从其内源性抑制剂Hexim 1和7SK snRNA中释放出来，但不是与HIV达特协同作用所必需的。The EMBO Journal（2009）28，1407-1417. doi：10.1038/doj.2009.99; 2009年4月23日在线发布
The elongation competence of the RNA polymerase II complex is critically dependent on the positive transcription elongation factor b (P-TEFb). P-TEFb exists in two forms in cells, an active form composed of cyclin T1 and CDK9 and an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA. Here, we report that partitioning of active and inactive P-TEFb is regulated by acetylation of cyclin T1. Cyclin T1 acetylation triggers dissociation of Hexim1 and 7SK snRNA from cyclin T1/CDK9 and activates the transcriptional activity of P-TEFb. This activation is lost in P-TEFb complexes containing cyclin T1 that can no longer be acetylated. An acetylation-deficient cyclin T1 mutant dominantly suppresses NF-kappa B-mediated activation of the interleukin-8 promoter but continues to synergize normally with the HIV Tat protein to transactivate the HIV long terminal repeat. These findings support the model that acetylation of cyclin T1 serves as a physiological switch that liberates P-TEFb from its endogenous inhibitors Hexim1 and 7SK snRNA, but is not required for the cooperative action with HIV Tat. The EMBO Journal (2009) 28, 1407-1417. doi:10.1038/emboj.2009.99; Published online 23 April 2009