P53 Damage and Carcinogenicity
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing p53 in humans through the SV40 Large T-antigen and SV40 Small T-antigen. p53 is responsible for initiating regulated cell death ("apoptosis"), or cell cycle arrest when a cell is damaged. A mutated p53 gene may contribute to uncontrolled cellular proliferation, leading to a tumor.
SV40 may act as a co-carcinogen with crocidolite asbestos to cause both Peritoneal and Pleural Mesothelioma (review ).
When SV40 infects nonpermissive cells, such as 3T3 mouse cells, the dsDNA of SV40 becomes covalently integrated. In nonpermissive cells only the early gene expression occurs and this leads to transformation, or oncogenesis. The nonpermissive host needs the Large T-antigen and the Small t-antigen in order to function. The Small T-antigen interacts with and integrates with the cellular phosphatase pp2A. This causes the cell to lose the ability to initiate transcription.
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