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SV40 small T antigen and PP2A phosphatase in cell transformation

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Abstract

The SV40 early region protein, SV40 small t antigen, promotes cell transformation through negative regulation of the protein phosphatase 2A (PP2A) family of serine–threonine phosphatases. More recently, reduced levels of PP2A activity have been found in different types of human cancer. This occurs either through inactivating mutations of PP2A structural subunits, or by upregulation of the cellular PP2A inhibitors, CIP2A and SET. Several distinct PP2A complexes have been identified that contribute directly to tumor suppression by regulating specific phosphorylation events. These studies provide us with new insights into the role of protein phosphatases in cancer initiation and maintenance.

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Abbreviations

APC:

adenomatous polyposis coli

CIP2A:

cancerous inhibitor of PP2A

CREB:

cAMP-responsive element binding protein

ERK:

extracellular signal-regulated kinase

HEAT:

Huntingtin, elongation factor 3, PP2A A subunit, and TOR kinase

HPV:

human papillomavirus

hTERT:

human telomerase catalytic subunit

KSR:

kinase suppressor of Ras

LT:

large T antigen

MAPK:

mitogen-activated protein kinase

NFkB:

nuclear factor kappa B

PI3K:

phosphatidylinositol 3-kinase

PP2A:

protein phosphatase type 2A

ST:

small T antigen

SV40:

simian virus 40

TOR:

target of rapamycin

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Acknowledgements

We thank the members of the Hahn laboratory for the helpful discussions. This work was supported in part by a grant from the U.S. National Cancer Institute P01 CA50661 (WCH).

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Authors and Affiliations

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

    Anna A. Sablina & William C. Hahn

  2. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 44 Binney Street, Boston, MA, 02115, USA

    Anna A. Sablina & William C. Hahn

  3. Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA

    Anna A. Sablina & William C. Hahn

  4. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA, 02142, USA

    William C. Hahn

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Correspondence to William C. Hahn.

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Sablina, A.A., Hahn, W.C. SV40 small T antigen and PP2A phosphatase in cell transformation. Cancer Metastasis Rev 27, 137–146 (2008). https://doi.org/10.1007/s10555-008-9116-0

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