title: Cyclin K functions as a CDK9 regulatory subunit and participates in RNA polymerase II transcription.
abstract: 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.
authors.affiliation: Department of Biology, Tularik Inc., South San Francisco, California 92080, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Fu
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.forename: G
authors.initials: G
authors.lastname: Lee
authors.forename: D H
authors.initials: DH
authors.lastname: Price
authors.forename: O
authors.initials: O
authors.lastname: Flores
mesh_terms: 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
chemical_list: C113028:CCNK protein, human; D016213:Cyclins; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II