Cyclin C CDK8 and cyclin H CDK7 p36 are biochemically distinct CTD kinases

被引:100
作者
Rickert, P
Corden, JL
Lees, E
机构
[1] DNAX Res Inst Mol & Cellular Biol Inc, Dept Cell Signaling, Palo Alto, CA 94304 USA
[2] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21209 USA
关键词
cyclin C; CDK8; CTD; RNA polymerase II;
D O I
10.1038/sj.onc.1202399
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phosphorylation of the carboxyl-terminal domain (CTD) of RNA polymerase IT is important for basal transcriptional processes in vivo and for cell viability. Several kinases, including certain cyclin-dependent kinases, can phosphorylate this substrate in vitro. It has been proposed that differential CTD phosphorylation by different kinases may regulate distinct transcriptional processes. We have found that two of these kinases, cyclin C/CDK8 and cyclin H/CDK7/p36, can specifically phosphorylate distinct residues in recombinant CTD substrates, This difference in specificity may be largely due to their varying ability to phosphorylate lysine-substituted heptapeptide repeats within the CTD, since they phosphorylate the same residue in CTD consensus heptapeptide repeats. Furthermore, this substrate specificity is reflected in vivo where cyclin C/CDK8 and cyclin H/CDK7/p36 can differentially phosphorylate an endogenous RNA polymerase II substrate, Several small-molecule kinase inhibitors have different specificities for these related kinases, indicating that these enzymes have diverse active-site conformations. These results suggest that cyclin C/CDK8 and cyclin H/CDK7/p36 are physically distinct enzymes that may have unique roles in transcriptional regulation mediated by their phosphorylation of specific sites on RNA polymerase II.
引用
收藏
页码:1093 / 1102
页数:10
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