Role for PP2A in ARF signaling to p53.
Activation of the ARF-p53 tumor suppressor pathway is one of the cell's major defense mechanisms against cancer induced by oncogenes. The ARF-p53 pathway is dysfunctional in a high proportion of human cancers. The regulation of the ARF-p53 signaling pathway has not yet been well characterized. In this study polyoma virus (Py) is used as a tool to better define the ARF-p53 signaling pathway. Py middle T-antigen (PyMT) induces ARF, which consequently up-regulates p53. We show that Py small T-antigen (PyST) blocks ARF-mediated activation of p53. This inhibition requires the small T-antigen PP2A-interacting domain. Our results reveal a previously unrecognized role of PP2A in the modulation of the ARF-p53 tumor suppressor pathway.
Moule
Madeleine G
MG
UCSF Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94143-0128, USA.
Collins
Crista H
CH
McCormick
Frank
F
Fried
Mike
M
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D002472:Cell Transformation, Viral; D004249:DNA Damage; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts; D019085:Fluorescent Antibody Technique, Direct; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D000952:Antigens, Polyomavirus Transforming; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D010749:Phosphoprotein Phosphatases