A COMPARISON OF THE BIOLOGICAL-ACTIVITIES OF WILD-TYPE AND MUTANT-P53

Tumorigenesis is characterized by a series of genetic alterations in both dominant oncogenes and tumor suppressor genes. A hallmark of tumor suppressor genes is that both alleles are generally altered during transformation, which usually represents a loss of function phenotype. The p53 tumor suppressor gene is the most frequently affected gene detected in human cancer. There is now growing evidence suggesting that mutation of p53 may involve not only a loss of function of wild-type p53 activity but also a gain of function phenotype contributed by the mutant p53 protein. The study of the biological properties and functions of both wild-type and mutant p53 is central to our understanding of human cancer. These properties and functions of wild-type and mutant p53 will be compared and contrasted here and elsewhere within this thematic issue. In addition, the mechanisms of inactivation of p53 function, which include: 1) mutation, 2) inhibition by viral oncogene products, 3) inhibition by cellular regulators, and 4) alteration in subcellular localization, will be discussed.