The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth

The tumor suppressor p53 plays a central role in the protection against DNA damage and other forms of physiological stress primarily by inducing cell cycle arrest or apoptosis. Mutation of p53, which is the most frequent gene tic alteration detected in human cancers, inactivates these growth regulato ry functions and causes a loss of tumor suppressor activity. In some cases, mutation also confers tumor-promoting functions, such as the transcription al activation of genes involved in cell proliferation, cell survival and an giogenesis. Consequently, cells expressing some forms of mutant p53 show en hanced tumorigenic potential with increased resistance to chemotherapy and radiation. Our current understanding of these activities is summarized in t his review. By dissecting out mechanistic differences between wild-type and mutant p53 activities, it may be possible to develop therapeutics that res tore tumor suppressor function to mutant p53 or that selectively inactivate mutant p53 tumor-promoting functions. (C) 2001 Published by Elsevier Scien ce B.V.