生物
细胞周期蛋白D
细胞周期蛋白A2
细胞周期蛋白
细胞周期蛋白依赖激酶复合物
分子生物学
细胞周期蛋白依赖激酶
RNA聚合酶Ⅱ
细胞生物学
周期素
细胞周期蛋白依赖激酶2
激酶
生物化学
细胞周期
基因表达
蛋白激酶A
基因
发起人
作者
Soo-Chen Cheng,Michael A. Kuzyk,Annie Moradian,Taka-Aki Ichu,Vicky C. Chang,Jerry F. Tien,Sarah Vollett,Malachi Griffith,Marco A. Marra,Gregg B. Morin
摘要
CrkRS (Cdc2-related kinase, Arg/Ser), or cyclin-dependent kinase 12 (CKD12), is a serine/threonine kinase believed to coordinate transcription and RNA splicing. While CDK12/CrkRS complexes were known to phosphorylate the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II), the cyclin regulating this activity was not known. Using immunoprecipitation and mass spectrometry, we identified a 65-kDa isoform of cyclin K (cyclin K1) in endogenous CDK12/CrkRS protein complexes. We show that cyclin K1 complexes isolated from mammalian cells contain CDK12/CrkRS but do not contain CDK9, a presumed partner of cyclin K. Analysis of extensive RNA-Seq data shows that the 65-kDa cyclin K1 isoform is the predominantly expressed form across numerous tissue types. We also demonstrate that CDK12/CrkRS is dependent on cyclin K1 for its kinase activity and that small interfering RNA (siRNA) knockdown of CDK12/CrkRS or cyclin K1 has similar effects on the expression of a luciferase reporter gene. Our data suggest that cyclin K1 is the primary cyclin partner for CDK12/CrkRS and that cyclin K1 is required to activate CDK12/CrkRS to phosphorylate the CTD of RNA Pol II. These properties are consistent with a role of CDK12/CrkRS in regulating gene expression through phosphorylation of RNA Pol II.
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