Forms and functions of p53

Abstract

There is evidence that wild-type p53 can both promote and suppress cell proliferation and these opposing functions correlate with alternative conformations of the p53 protein. In the light of more recent evidence I now propose that wild-type p53 can adopt at least three different forms, each of which correlates with a defined function in cell growth control. The three forms are most simply defined by reactivity with two monoclonal antibodies, PAb421 and PAb1620. One form (421 degrees/1620+) suppresses cell growth and maintains quiescence, and a second form (421+/1620 degrees) activates and promotes cell proliferation. The third form (421+/1620+) acts as a differential sensor for incoming positive and negative growth regulatory signals and can be converted either to the suppressor or to the promoter form for cell growth. Regulation of p53 tertiary structure involves redox modulation and phosphorylation, and offers a novel rationale for anti-cancer therapy.