title: Role for PP2A in ARF signaling to p53.
abstract: 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.
authors.affiliation: UCSF Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94143-0128, USA.
authors.forename: Madeleine G
authors.initials: MG
authors.lastname: Moule
authors.forename: Crista H
authors.initials: CH
authors.lastname: Collins
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
authors.forename: Mike
authors.initials: M
authors.lastname: Fried
mesh_terms: 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
chemical_list: D000952:Antigens, Polyomavirus Transforming; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D010749:Phosphoprotein Phosphatases