Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II.
A number of cyclin/kinase complexes have been identified in mammalian cells that are essential for controlled cell proliferation. Cyclin C was isolated by virtue of its ability to rescue the triple CLN mutation in yeast; however, until now its function has remained unclear. Cyclin C associates with a novel cyclin dependent kinase, CDK8, and we demonstrate that this complex is associated with kinase activity towards the carboxy-terminal domain (CTD) of RNA polymerase II. We have identified at least two distinct cyclin C/CDK8 containing complexes within the cell, a larger complex over 500 kD in size, that also contains the largest subunit of RNA polymerase II, and a smaller 170 kD species. Both of these cyclin C complexes retain potent CTD kinase activity. We further demonstrate that the cyclin C/CDK8 complex associates with the large subunit of RNA polymerase II in vivo, implicating a potential role for cyclin C/CDK8 in regulating its activities.
Rickert
P
P
DNAX Research Institutte of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Seghezzi
W
W
Shanahan
F
F
Cho
H
H
Lees
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D056745:Cyclin C; D056748:Cyclin H; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000276:immunology / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C503674:CCNC protein, human; C534751:CCNH protein, human; C503675:Ccnc protein, mouse; C534752:Ccnh protein, mouse; D056745:Cyclin C; D056748:Cyclin H; D016213:Cyclins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C093345:SSN8 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; C498309:SSN3 protein, S cerevisiae; D012319:RNA Polymerase II; D000095043:Cyclin-Dependent Kinase-Activating Kinase