Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription.
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.
Fu
T J
TJ
Department of Biology, Tularik Inc., South San Francisco, California 92080, USA.
Peng
J
J
Lee
G
G
Price
D H
DH
Flores
O
O
D002850:Chromatography, Gel; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
C113028:CCNK protein, human; D016213:Cyclins; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II