E1A oncogene-induced cellular sensitization to immune-mediated apoptosis is independent of p53 and resistant to blockade by E1B 19 kDa protein.
E1A oncogene expression sensitizes mammalian cells to apoptosis triggered by cytolytic lymphocytes (CL) [16]. Most studies suggest that E1A-induced apoptosis involves a p53-dependent cellular pathway that is blocked by the E1B 19 kDa gene product. In this study, the roles of p53 and E1B 19 kDa were tested for E1A sensitization to CL-induced apoptosis in contrast with apoptosis triggered by TNF alpha or chemical injuries. E1A sensitization to immune-mediated (CL- or TNF-induced) apoptosis was independent of p53 expression and was resistant to blockade by E1B 19 kDa protein in mouse and hamster cells. In contrast, the p53 requirement for chemically induced apoptosis of E1A-sensitized cells varied with the agent used to treat cells. Apoptosis induced by diverse chemical agents (hygromycin, beauvericin, etoposide, H(2)O(2)) was blocked by E1B 19 kDa expression. Therefore, both the p53-dependence and the E1B 19 kDa blockade of E1A-induced cellular sensitization to apoptotic injury depend on the type of proapoptotic injury tested. These data suggest that the mechanisms by which E1A sensitizes tumor cells to immune-mediated apoptosis and to rejection by immunocompetent animals do not require cellular expression of wild-type p53 and can function independently of the Bcl-2-like, antiapoptotic mechanisms of E1B 19 kDa.
Cook
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JL
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA. jlcook@uic.edu
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D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D002934:Cinnamates; D006224:Cricetinae; D047630:Depsipeptides; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression; D016158:Genes, p53; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009857:Oncogenes; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D000900:Anti-Bacterial Agents; D002934:Cinnamates; D047630:Depsipeptides; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C004456:beauvericin; D006921:Hygromycin B; C026273:hygromycin A; D005047:Etoposide; D006861:Hydrogen Peroxide