Induction of apoptosis by adenovirus E4orf4 protein.
Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53-independent apoptosis in transformed cells, but not in normal cells. E4orf4-induced apoptosis can occur without activation of known caspases, although E4orf4 induces caspase activity in some cell lines. The interaction of E4orf4 with a specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B subunits, but not with those that contain B' subunits, is required for induction of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy, and discusses whether E4orf4-induced apoptosis plays a role in the viral life cycle. Future research directions are also highlighted.
The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. tamark@tx.technion.ac.il
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Kleinberger
D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C121517:E4orf4 protein, adenovirus; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D020169:Caspases