Normal and malignant growth control by p53

Abstract

The role of the p53 protein in the growth of both the normal and the transformed cell has been the focus of investigation since the discovery of p53 12 years ago. Although the function of this protein is not yet known, p53 appears to be a critical protein involved in the regulation of cell growth. Once classified as a dominant oncogene [1–3], it has recently become clear that only mutant forms of p53 can contribute to cellular transformation [4–6]. In contrast, overexpression of the wild-type p53 protein suppresses the formation of transformed cells [7,8] and, in addition, inhibits the growth of tumor cells [9–13]. These observations have resulted in the redefinition of the role of p53 to that of a recessive oncogene or a tumor suppressor gene [reviewed in 14,15]. Numerous studies conducted in the past few years have shown that alterations (deletions, rearrangements, missense mutations) in the p53 gene occur frequently (25–85% of the time) in quite a wide variety of human tumors [16–40]. Thus, mutations at the p53 locus are, at present, the most common genetic change known to occur in human cancer. Do certain mutations appear to be selected for in human tumors? What are the known activities and phenotypes of the p53 protein in the normal cell, and what is the effect of mutation on the known p53 properties? What is the role, if any, of the overexpressed mutant p53 proteins in the tumor cell?