A cyclin associated with the CDK-activating kinase MO15.
The eukaryotic cell cycle is regulated by the sequential activation of cyclin-dependent kinases (CDKs). CDK activation is dependent on cyclin binding and phosphorylation of a conserved threonine (T161 in Cdc2) mediated by the CDK-activating kinase CAK. A CDK-related kinase, MO15 (ref. 10), has been identified as the catalytic subunit of CAK (refs 11-13). Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein. Cyclin H is a major MO15 partner in vivo and enhances the kinase activity of MO15 towards Cdk2/cyclin A. These findings demonstrate that a cyclin/kinase complex can function as a regulator of other cyclin/kinase complexes, and suggest that cyclin/kinase cascades may exist.
Mäkelä
T P
TP
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Tassan
J P
JP
Nigg
E A
EA
Frutiger
S
S
Hughes
G J
GJ
Weinberg
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism*; D004247:DNA; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D014162:Transfection; D014981:Xenopus; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D011994:Recombinant Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase