p63 in Epithelial Survival, Germ Cell Surveillance, and Neoplasia

Abstract

The p53homolog p63has emerged as a gene with an enormously complex function that is distinct from that of p53. It encodes two distinct transcript isoforms that have a dramatic impact on replenishment of cutaneous epithelial stem cells and on ovarian germ cell survival. However, although these two fundamental roles of p63 attest to its powerful place in development, its other functions—specifically the apparent capacity of p63, when induced, to supervise the emergence of new cell populations in the breast, prostate, cervix, and upper reproductive tract—are shared by embryo and adult. These observed functions may only scratch the surface of a repertoire that has been postulated to encompass a range of cellular activities, as evidenced by the fact that p63 proteins have been shown to potentially bind to over 5800 target sites. Whether tumorigenic pathways are also involved, and to what extent, is a subject of both promise and controversy that remains to be resolved.