ONCOGENIC POTENTIAL OF THE ADENOVIRUS E4ORF6 PROTEIN

The group C adenovirus E4orf6 protein has previously been shown to bin d to the p53 cellular tumor suppressor protein and block its ability t o activate transcription. Here we show that the E4orf6 protein blocks the induction of p53-mediated apoptosis when AT6 cells, which harbor a temperature-sensitive p53, are shifted to the permissive temperature. The E4orf6 protein does not, however, prevent the induction of apopto sis in p53-deficient H1299 cells by treatment with tumor necrosis fact or ru and cycloheximide. The E4orf6 protein also cooperates with the a denovirus E1A protein to transform primary baby rat kidney cells, and it cooperates with the adenovirus E1A plus E1B 19-kDa and E1B 55-kDa p roteins to increase the number of baby rat kidney cell transformants a nd enhance the rate at which they arise. The level of p53 is substanti ally reduced in transformed cells expressing the E4orf6 protein in com parison to adenovirus transformants lacking it. The E4orf6 gene also a ccelerates tumor formation when transformed baby rat kidney cells are injected subcutaneously into the nude mouse, and it converts human 293 cells from nontumorigenic to tumorigenic in nude mice. In addition to the well-studied EIA and E1B oncogenes, group C adenoviruses harbor a third oncogene, E4orf6, which functions in some respects similarly to the E1B oncogene.