Biochemical Characterization of Complexes with p21, a CDK Inhibitor
Annual rept. 1 Aug 1996-31 Jul 1997
HARVARD UNIV CAMBRIDGE MA
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The cyclin-dependent kinases CDKs are of pivotal importance for driving cell proliferation. The p2lWAFl protein, by contrast, belongs to a family of growth regulators that are thought to restrain cell growth primarily as a consequence of their ability to inhibit CDKs. In vivo, p2l is known to form stable, higher order complexes with cyclin-dependent kinases and the DNA polymerase processivity factor, PCNA. As an important downstream target of the p53 checkpoint gene, p21 is thought to execute a critical growth arrest function in response to DNA damage and other cellular stress and differentiation signals. In addition, loss of p21 function may be associated with cellular transformation in some settings. Despite this information, it is not yet clear how p21 functions in vivo to regulate the multiple complexes with which it associates. Nor is it clear how p21 specifically regulates CDKs in vivo or whether all components of p21 complexes have been identified. Given the role of p21 and related proteins in kinase inhibition and growth control, a full understanding of the mechanisms used by this protein to restrain proliferation may yield clues toward the therapeutic intervention in breast cancer.
- Medicine and Medical Research