Association of the cell cycle regulatory proteins p45(SKP2) and CksHs1. Functional effect on CDK2 complex formation and kinase activity.
In mammalian cells, CDK2 is part of a multiprotein complex that includes Cyclin A or E and cell cycle regulatory proteins such as p21(Cip1), PCNA, p27(Kip1), p45(SKP2), p19(SKP1), and CksHs1/CksHs2. While the role of some of these proteins has been well studied, the function of other proteins in the complex remains unclear. In this study, we showed that the carboxyl-terminal region of p45(SKP2) associates directly with CksHs1 and that CksHs1 negatively regulated the interaction between p45(SKP2) and CDK2. Moreover, we showed that overexpression of CksHs1 inhibits CDK2 kinase activity and that additional expression of p45(SKP2) overcame this inhibition and restored CDK2 kinase activity. We proposed that the association of CksHs1 and p45(SKP2) prevented CksHs1 from binding CDK2 and negatively regulating the CDK2 kinase activity.
Mongay
L
L
Servei d'Immunologia, Hospital Clínic i Provincial de Barcelona, Villarroel 170, Barcelona 08036, Spain.
Plaza
S
S
Vigorito
E
E
Serra-Pagès
C
C
Vives
J
J
D000818:Animals; D042846:CDC2-CDC28 Kinases; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011485:Protein Binding; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D044786:S-Phase Kinase-Associated Proteins; D014162:Transfection
C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D044786:S-Phase Kinase-Associated Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases