P73-BETA, UNLIKE P53, SUPPRESSES GROWTH AND INDUCES APOPTOSIS OF HUMAN-PAPILLOMAVIRUS E6-EXPRESSING CANCER-CELLS

Human papillomavirus (HPV) is the major cause of cervical cancer world wide. HPV-E6 protein targets the p53 tumor suppressor protein for degr adation by ubiquitin-mediated proteolysis making such cancers resistan t to p53-gene therapy. Here we show that infection of human cancer cel ls by E6-expressing adenovirus (Ad-E6) leads to degradation of both wi ld-type or mutant p53 protein. Interestingly, the p53-homologue candid ate tumor suppressor p73 is not degraded in Ad-E6 infected cancer cell s. Wild-type p73 beta and not wild-type p53 or mutant p73 is a potent inhibitor of cancer colony growth and inducer of apoptosis, despite HP V-E6 overexpression. The results suggest a novel strategy using p73 be ta in gene therapy of HPV-E6 expressing cancers.