Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B.
Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of which independently cooperate with E1A. E1B 19K or 55K protein, or the human Bcl-2 protein, functions to suppress apoptosis and thereby permits transformation with E1A. The E1B 55K protein blocks p53 tumor suppressor protein function, indicating that p53 may mediate apoptosis by E1A. In the mutant conformation, p53 blocked induction of apoptosis by E1A and efficiently cooperated with E1A to transform primary cells. When p53 was returned to the wild-type conformation, E1A+p53 transformants underwent cell death by apoptosis. This induction of apoptosis by conformational shift of p53 from the mutant to the wild-type form was inhibited by expression of the E1B 19K protein. Thus, the p53 protein may function as a tumor suppressor by initiating a cell suicide response to deregulation of growth control by E1A. E1B 19K and 55K proteins provide separate mechanisms that disable the cell suicide pathway of p53.
Debbas
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M
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854.
White
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E
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002472:Cell Transformation, Viral / Q000502:physiology*; D003587:Cytomegalovirus; D004249:DNA Damage; D004279:DNA, Viral; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D009154:Mutation; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53