The Role of P53 in Cell Cycle Regulation

The tumor suppressor gene p53, implicated in diverse types of human tumors, functions both as a gene-specific transcription factor as well as a specific inhibitor of the transcription of certain genes. The two physiological outcomes of re-expression of wild type p53 in tumor cells, not expressing wild type p53, are G1 arrest and apoptosis. The mechanism of G1 arrest by p53 is much better documented than its ability to trigger apoptosis. P53 as a transcription factor induces the expression of p21WAF1/CIP1/Sdi1, an inhibitor of the cyclin dependent kinases (CDKs)2, 3, 4 and 6. Thus, a G1 arrest can result simply by the p53 induced expression of p21WAF1/CIP1/Sdi1. Amongst the other genes presently characterized to be regulated by p53 are BAX, a homologue of the BCL-2 gene. Bax does not trigger apoptosis, but simply accelerates the rate at which apoptosis proceeds54. P53 also down regulates the expression of cyclin A, providing a secondary break on cell cycle progression into the through the S phase.