DISPENSABILITY OF P53 DEGRADATION FOR TUMORIGENICITY AND DECREASED SERUM REQUIREMENT OF HUMAN PAPILLOMAVIRUS TYPE-16E6

Certain types of human papillomavirus (HPV), such as types 16 and 18, are etiological agents for carcinogenesis of the uterine cervix. These HPVs have two oncogenes, E6 and E7, that have transforming activities in established murine cells. Tumorigenicity and decreased serum requi rement for cell growth are conferred by the E6 gene, whereas anchorage -independent growth is mainly governed by the E7 gene. To understand t he mechanism of cellular transformation by the HPV16 E6 gene, we exami ned three mutant E6 proteins defective for p53 binding, p53 degradatio n, or transactivation of the adenovirus E2 promoter for the ability to induce tumorigenicity and decreased serum requirement. The results sh owed that tumorigenicity and decreased serum requirement were associat ed with the ability of E6 to bind to p53, although the subsequent degr adation of p53 was not required for these functions. (C) 1998 Wiley-Li ss, Inc.