Human Cyclin K, a Novel RNA Polymerase II-Associated Cyclin Possessing Both Carboxy-Terminal Domain Kinase and Cdk-Activating Kinase Activity

ABSTRACT

The gene coding for human cyclin K was isolated as aCPR (cell-cycle progression restoration) gene by virtue of its ability to impart a Far⁻ phenotype to the budding yeast Saccharomyces cerevisiae and to rescue the lethality of a deletion of the G₁ cyclin genes CLN1,CLN2, and CLN3. The cyclin K gene encodes a 357-amino-acid protein most closely related to human cyclins C and H, which have been proposed to play a role in regulating basal transcription through their association with and activation of cyclin-dependent kinases (Cdks) that phosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAP II). Murine and Drosophila melanogaster homologs of cyclin K have also been identified. Cyclin K mRNA is ubiquitously expressed in adult mouse and human tissues, but is most abundant in the developing germ cells of the adult testis and ovaries. Cyclin K is associated with potent CTD kinase and Cdk kinase (CAK) activity in vitro and coimmunoprecipitates with the large subunit of RNAP II. Thus, cyclin K represents a new member of the “transcription” cyclin family which may play a dual role in regulating Cdk and RNAP II activity.

ACKNOWLEDGMENTS

We thank Wade Harper and members of the Elledge lab for comments, helpful discussions, and reagents. We also thank the Baylor FISH Core Facility and Vesna Jurecic for mapping CPR4. We thank E. Nigg for communicating results before publication.

M.C.E. is supported by the National Institutes of Health Medical Scientist Training Program at Baylor College of Medicine. This work was supported by grant GM44664 from the Public Health Service to S.J.E. S.J.E. is a PEW Scholar in Biomedical Sciences and an Investigator of the Howard Hughes Medical Institute.