CLONING AND FUNCTIONAL-ANALYSIS OF HUMAN P51, WHICH STRUCTURALLY AND FUNCTIONALLY RESEMBLES P53

The p53 tumor suppressor gene, which is induced by DNA damage and/or s tress stimuli, causes cells to undergo G1-arrest or apoptotic death; t hus it plays an essential role in human carcino-genesis(1,2). We have searched for p53-related genes by using degenerate PCR, and have ident ified two cDNA fragments similar to but distinct from p53: one previou sly reported, p73 (refs. 3,4), and the other new. We cloned two major splicing variants of the latter gene and named these p51A and p51B(a h uman homologue of rat Ket). The p51A gene encodes a 448-amino-acid pro tein with a molecular weight of 50.9 kDa; and p51B, a 641-amino-acid p rotein with a molecular weight of 71.9 kDa. In contrast with the ubiqu itous expression of p53, expression of p51 mRNA was found in a limited number of tissues, including skeletal muscle, placenta, mammary gland , prostate, trachea, thymus, salivary gland, uterus, heart and lung. I n p53-deficient cells, p51A induced growth-suppression and apoptosis, and upregulated p21(waf-1) through p53 regulatory elements. Mutations in p51 were found in some human epidermal tumors.