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Biochemical Characterization of Complexes with p21, a CDK Inhibitor
Annual rept. 1 Aug 1997-31 Jul 1998
HARVARD UNIV CAMBRIDGE MA
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Cell cycle progression and proliferation are mediated by the cyclin-dependent kinases CDKs. These growth-promoting factors are counter-balanced by another family of inhibitory proteins that includes p21WAF1, a regulator that is thought to restrain cell growth primarily as a consequence of its ability to inhibit CDKs. It is known that p21 assembles into multiple complexes with CDKs and the DNA polymerase perceptivity factor, PCNA, in vivo, but despite this knowledge, the reason for the existence of diverse complexes with p21 is not clear. In addition, the activity of p21-CDK complexes in vivo has been controversial, since there have been reports of p21-CDK complexes that retain kinase activity. Moreover, it is not known whether all components of p21 complexes have been identified. Given the role of p21 as a downstream target of the p53 checkpoint protein and the role of this protein and related ones in kinase inhibition and growth control, we seek to understand how p21 function is related to normal cell growth and whether loss of function results in transformation of human mammary cells.
APPROVED FOR PUBLIC RELEASE