Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C.
Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals.
Tassan
J P
JP
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Jaquenoud
M
M
Léopold
P
P
Schultz
S J
SJ
Nigg
E A
EA
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002474:Cell-Free System; D003001:Cloning, Molecular; D056745:Cyclin C; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000145:classification / Q000235:genetics; D016213:Cyclins / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
C503674:CCNC protein, human; D056745:Cyclin C; D016213:Cyclins; D018076:DNA, Complementary; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; C498309:SSN3 protein, S cerevisiae