Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription

Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription
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DOI:
10.1074/jbc.274.49.34527
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发表时间:
1999-12-03
影响因子:
4.8
通讯作者:
Flores, O
Flores, O
中科院分区:
生物学2区
文献类型:
--
作者:
Fu, TJ;Peng, JM;Flores, O

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在理解RNA聚合酶II (RNAPII)的伸长控制方面的重要进展来自于最近对正转录伸长因子b (P-TEFb)的鉴定,并证明该因子是一种蛋白激酶,可磷酸化RNAPII最大亚基的羧基末端结构域(CTD)。从哺乳动物细胞中分离的P-TEFb复合体含有催化亚基(CDK9),细胞周期蛋白亚基(细胞周期蛋白T1或细胞周期蛋白T2),以及其他尚未确定的,为了确定参与P-TEFb功能的其他因素,我们以CDK9为诱饵进行酵母双杂交筛选,发现cyclin K在体内与CDK9相互作用,生化分析表明,cyclin K作为CDK9的调控亚基,CDK9-cyclin K复合物磷酸化RNAPII的CTD,并在体外转录反应中功能取代由CDK9和cyclin T组成的P-TEFb。
Important progress in the understanding of elongation control by RNA polymerase II (RNAPII) has come from the recent identification of the positive transcription elongation factor b (P-TEFb) and the demonstration that this factor is a protein kinase that phosphorylates the carboxyl-terminal domain (CTD) of the RNAPII largest subunit, The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function, To identify additional factors involved in P-TEFb function we performed a yeast two-hybrid screen using CDK9 as bait and found that cyclin K interacts with CDK9 in vivo, Biochemical analyses indicate that cyclin K functions as a regulatory subunit of CDK9, The CDK9-cyclin K complex phosphorylated the CTD of RNAPII and functionally substituted for P-TEFb comprised of CDK9 and cyclin T in in vitro transcription reactions.