P21 - NEGATIVE REGULATOR OF THE CELL-CYCLE

Progression through the cell cycle is regulated by cyclins and cyclin- dependent kinases (Cdks), The cyclin kinase inhibitor p21 (also known as WAF1, CIP1, SDI1, and MDA-B) can induce G1 arrest and block entry i nto S phase by inactivating Cdks or by inhibiting activity of prolifer ating cell nuclear antigen (PCNA), In normal cells, p21 exists in quat ernary complexes with cyclin, Cdk, and PCNA, Transcription of the p21 gene is activated by p53-dependent and -independent mechanisms, Mice d eficient in p21 exhibit no apparent phenotype, although p21 function h as been demonstrated to be necessary for p53-mediated G1 arrest follow ing irradiation of p21-deficient mouse embryonic fibroblasts. Thus, th e function of p21 under normal circumstances appears to be redundant, p21 is expressed in terminally differentiating cells of a variety of t issues in a p53-independent manner, Overexpression of p21 results in G 1 arrest and has been shown to suppress effectively tumor growth in vi tro and in vivo. We review the recent literature describing the functi onal characterization of p21. This protein plays a key role in regulat ing the cell cycle and may have potential gene therapy applications.