Induction of Non-classical Cancer Cell-specific Apoptosis by the Adenovirus E4orf4 Protein

• 作 者: TamarKleinberger;
• 机 构: Department of Microbiology Faculty of Medicine Technion Israel
• 出 处: BIT Life Sciences' 1st Annual World Cancer Congess-2008(
• 发表日期: 2008年期

　　The adenovirus E4orf4 protein induces apoptosis in transformed cells.Cell death induced by E4orf4 is unique by at least three criteria.1) Oncogenic transformation of primary cells in tissue culture sensitizes them to cell killing by E4orf4, indicating that E4orf4 research may have exciting implications for cancer therapy.2) E4orf4-induced cell death does not require the presence of the p53 tumor suppressor gene, and could thus occur in p53-deficient cancer cells.3) E4orf4-induced apoptosis is caspase-independent in many cell lines, and is thus non-classical.Instead of a dependence on caspases, E4orf4-induced apoptosis requires an interaction of the viral protein with a cellular phosphatase called PP2A.E4orf4 also associates with kinases of the Src family, and this interaction enhances cell death.The three unique features of E4orf4-induced apoptosis suggest that the E4orf4-initiated pathway includes components that respond differentially to the E4orf4 signal in cancer and normal cells, and are not part of the widelystudied classical apoptotic pathways.