Interaction between Cdc37 and Cdk4 in human cells.
Using the yeast two-hybrid system we have identified novel potential Cdk4 interacting proteins. Here we described the interaction of Cdk4 with a human homologue of the yeast Drosophila CDC37 gene products. Cdc37 protein specifically interacts with Cdk4 and Cdk6, but not with Cdc2, Cdk2, Cdk3, Cdk5 and any of a number of cyclins tested. Cdc37 is not an inhibitor nor an activator of the Cdk4/cyclin D1 kinase, while it appears to facilitate complex assembly between Cdk4, and cyclin D1 in vitro. Cdc37 competes with p16 for binding to Cdk4, suggesting that p16 might exert part of its inhibitory function by affecting the formation of Cdk4/cyclin D1 complexes via Cdc37.
Lamphere
L
L
Mitotix, Inc., Cambridge, Massachusetts 02139, USA.
Fiore
F
F
Xu
X
X
Brizuela
L
L
Keezer
S
S
Sardet
C
C
Draetta
G F
GF
Gyuris
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D018833:Chaperonins; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
C513270:CDC37 protein, S cerevisiae; C498362:CDC37 protein, human; C088085:Cdc37 protein, Drosophila; D018797:Cell Cycle Proteins; D016213:Cyclins; D029721:Drosophila Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D019938:Cyclin D1; C495900:CDK4 protein, human; C495896:Cdk4 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D018833:Chaperonins