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Cellular targets for SV40 large T-antigen.

D P Lane, V Simanis, R Bartsch

    Proceedings of the Royal Society of London. Series B, Biological Sciences
    |October 22, 1985
    PubMed
    Summary
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    Simian virus 40 (SV40) Large T-antigen drives tumor formation by integrating into host DNA and affecting cellular processes. It binds to specific DNA sites and the p53 protein, altering its cellular location and contributing to oncogenesis.

    Area of Science:

    • Virology
    • Oncology
    • Molecular Biology

    Background:

    • Simian virus 40 (SV40) infection induces tumors and transforms eukaryotic cells.
    • Viral DNA integration and expression of Large T-antigen are key to transformation.
    • Large T-antigen is essential for inducing and maintaining the transformed cellular state.

    Purpose of the Study:

    • To investigate the mechanisms by which SV40 Large T-antigen mediates cellular transformation and oncogenesis.
    • To identify cellular DNA sequences and proteins targeted by SV40 Large T-antigen.
    • To characterize the interaction between SV40 Large T-antigen and the p53 protein.

    Main Methods:

    • Utilizing a novel immunochemical procedure to isolate SV40 Large T-antigen bound DNA sequences in chromatin.

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  • Employing a range of monoclonal antibodies to characterize p53 protein localization and modifications.
  • Constructing bacterial plasmids for the synthesis of Large T-antigen and p53 fusion proteins.

    • Main Results:

    • Identified cellular DNA sequences with high-affinity binding sites for SV40 Large T-antigen, associated with transformed cells.
    • Demonstrated that SV40 Large T-antigen binds to and stabilizes the p53 protein.
    • Showed p53 protein shifts from the cytoplasm in normal cells to the nucleus in transformed cells, with one antibody recognizing a Large T-stabilized epitope.

    Conclusions:

    • SV40 Large T-antigen's oncogenic activity involves specific interactions with host cell DNA and the p53 protein.
    • The altered localization and stabilization of p53 by Large T-antigen are critical events in SV40-mediated transformation.
    • Understanding these interactions provides insights into oncogene action and viral oncogenesis.