P63, A P53 HOMOLOG AT 3Q27-29, ENCODES MULTIPLE PRODUCTS WITH TRANSACTIVATING, DEATH-INDUCING, AND DOMINANT-NEGATIVE ACTIVITIES

We describe the cloning of p63, a gene at chromosome 3q27-29 that bear s strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, includ ing proliferating basal cells of epithelial layers in the epidermis, c ervix, urothelium, and prostate. Unlike p53, the p63 gene encodes mult iple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 isotypes in many epithelial tissues lack an acidic N terminus corresp onding to the transactivation domain of p53. We demonstrate that these truncated p63 variants can act as dominant-negative agents toward tra nsactivation by p53 and p63, and we suggest the possibility of physiol ogical interactions among members of the p53 family.