Multiple pathways regulated by the tumor suppressor PP2A in transformation.
Reversible protein phosphorylation plays a central role in regulating intracellular signaling. Dysregulation of the mechanisms that regulate phosphorylation plays a direct role in cancer initiation and maintenance. Although abundant evidence supports the role of kinase oncogenes in cancer development, recent work has illuminated the role of specific protein phosphatases in malignant transformation. Protein phosphatase 2A (PP2A) is the major serine-threonine phosphatase in mammalian cells. Inactivation of PP2A by viral oncoproteins, mutation of specific subunits or overexpression of endogenous inhibitors contributes to cell transformation by regulating specific phosphorylation events. Here, we review recent progress in our understanding of how PP2A regulates mitogenic signaling pathways in cancer pathogenesis and how PP2A activity is modulated in human cancers.
Westermarck
Jukka
J
Institute of Medical Technology, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland.
Hahn
William C
WC
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D015513:Oncogene Proteins; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins; D054648:Protein Phosphatase 2