The tumor suppressor protein p53: a receptor to genotoxic stress that controls cell growth and survival

Abstract

The p53 protein is a transcription regulator that is frequently altered by mutation in cancer. Breakthroughs on two fronts shed light on its role in tumor suppression. First, a flurry of biochemical and structural studies (including a partial crystal structure) has sharpened the picture of p53 topology and functional properties. Second, downstream effectors of p53 have been identified including p21Waf-1/Cip-1, an inhibitor of cyclin-dependent kinases, and bax, a dominant-negative inhibitor of bcl-2. This suggest a scenario in which p53 is activated by genotoxic stress and regulates the transcription of at least two sets of genes. One is responsible for transient cell arrest in G1 and the other controls the initiation of apoptosis. Both processes eliminate potential oncogenic mutations, either by proper DNA repair or by inducing damaged cells to commit suicide.