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Involvement of PP2A in viral and cellular transformation

Oncogene volume 24, pages 7746–7755 (2005)Cite this article

Abstract

Although the small DNA tumor virus SV40 (simian virus 40) fails to replicate in human cells, understanding how SV40 transforms human and murine cells has and continues to provide important insights into cancer initiation and maintenance. The early region of SV40 encodes two oncoproteins: the large T (LT) and small t (ST) antigens. SV40 LT contributes to murine and human cell transformation in part by inactivating the p53 and retinoblastoma protein tumor suppressor proteins. SV40 ST inhibits the activity of the protein phosphatase 2A (PP2A) family of serine–threonine phosphatases, and this interaction is required for SV40-mediated transformation of human cells. PP2A regulates multiple signaling pathways, suggesting many possible targets important for viral replication and cell transformation. Genetic manipulation of particular PP2A subunits has confirmed a role for specific complexes in transformation, and recent work implicates the perturbation of the phosphatidylinositol 3-kinase/Akt pathway and c-Myc stability in transformation by ST and PP2A. Mutations in PP2A subunits occur at low frequency in human tumors, suggesting that alterations of PP2A signaling play a role in both experimentally induced and spontaneously arising cancers. Unraveling the complexity of PP2A signaling will not only provide further insights into cancer development but may identify novel targets with promise for therapeutic manipulation.

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Acknowledgements

JDA is a predoctoral fellow of the Howard Hughes Medical Institute. This work was supported in part by grants from the US National Cancer Institute K01 CA94223, P01 CA50661, and the Doris Duke Charitable Foundation to WCH.

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  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02115, MA, USA

    Jason D Arroyo & William C Hahn

  2. Department of Medicine, Brigham and Women's Hospital, Boston, 02115, MA, USA

    Jason D Arroyo & William C Hahn

  3. Departments of Pathology and Medicine, Harvard Medical School, Boston, 02115, MA, USA

    Jason D Arroyo & William C Hahn

  4. Broad Institute of Harvard and MIT, Cambridge, 02139, MA, USA

    William C Hahn

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Arroyo, J., Hahn, W. Involvement of PP2A in viral and cellular transformation. Oncogene 24, 7746–7755 (2005). https://doi.org/10.1038/sj.onc.1209038

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