The multi-tasking P-TEFb complex
The multi-tasking P-TEFb complex
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DOI：
10.1016/j.ceb.2008.04.008
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发表时间：
2008-06-01
影响因子：
7.5
通讯作者：
Jones, Katherine A.
中科院分区：
文献类型：
--
作者：
Bres, Vanessa;Yoh, Sunnie M.;Jones, Katherine A.
P - TEFb（CycT1 : Cdk9），后生动物RNA聚合酶II的丝氨酸2羧基末端结构域（CTD）激酶，在许多基因上调控转录延伸，并将mRNA合成与组蛋白修饰、前体mRNA加工以及mRNA输出整合在一起。P - TEFb被招募到靶基因需要H2B泛素化的去除、H3S10的磷酸化以及含溴结构域蛋白Brd4。Brd4在细胞周期的G1期激活生长相关基因，并且还能将P - TEFb连接到有丝分裂染色体上，可能是为了标记整个细胞分裂过程中活跃转录的位点。P - TEFb在反式激活和细胞转化过程中与c - Myc协同作用，并且还需要SKIP（c - Ski相互作用蛋白），一种mRNA延伸和剪接因子。P - TEFb/丝氨酸2磷酸化CTD的一些功能由Spt6转录延伸因子执行，Spt6转录延伸因子直接与磷酸化的CTD结合并招募Iws1（“与Spt6相互作用”）蛋白。反过来，Iws1与REF1/Aly核输出衔接蛋白相互作用并刺激mRNA输出的动力学。鉴于Spt6在调控染色质结构中的重要作用，结合CTD的Spt6 : Iws1复合物可能也在延伸过程中控制组蛋白修饰。转录之后，P - TEFb伴随成熟的mRNA进入细胞质以促进翻译延伸。
P-TEFb (CycT1:Cdk9), the metazoan RNA polymerase II Ser2 C-terminal domain (CTD) kinase, regulates transcription elongation at many genes and integrates mRNA synthesis with histone modification, pre-mRNA processing, and mRNA export. Recruitment of P-TEFb to target genes requires deubiquitination of H2Bub, phosphorylation of H3S10, and the bromodomain protein, Brd4. Brd4 activates growth-related genes in the G1 phase of the cell cycle and can also tether P-TEFb to mitotic chromosomes, possibly to mark sites of active transcription throughout cell division. P-TEFb co-operates with c-Myc during transactivation and cell transformation, and also requires SKIP (c-Ski-interacting protein), an mRNA elongation and splicing factor. Some functions of the P-TEFb/Ser2P CTD are executed by the Spt6 transcription elongation factor, which binds directly to the phosphorylated CTD and recruits the Iws1 ('interacts with Spt6') protein. Iws1, in turn, interacts with the REF1/Aly nuclear export adaptor and stimulates the kinetics of mRNA export. Given the prominent role of Spt6 in regulating chromatin structure, the CTD-bound Spt6:Iws1 complex may also control histone modifications during elongation. Following transcription, P-TEFb accompanies the mature mRNA to the cytoplasm to promote translation elongation.