Cell cycle control: a complex issue.
Do p27Kip1 and p21Cip1 function as activators or inhibitors of D cyclin-cdk4 activity? Attempts to answer this question, and thus to understand how cdk4--a key cell cycle regulator--becomes active, have produced conflicting data. In this perspective, we summarize the results of studies addressing the effects of p27Kip1 and p21Cip1 on the assembly and activation of D cyclin-cdk4 complexes. Emphasis is placed on our experimental findings that support a model of cell cycle control in which p27Kip1 and p21Cip1 stabilize D cyclin-cdk4 complexes but inhibit D cyclin-cdk4 activity.
Olashaw
Nancy
N
Molecular Oncology Program, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Bagui
Tapan K
TK
Pledger
W J
WJ
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005347:Fibroblasts; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases