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Titolo:
Polyoma virus disrupts ARF signaling to p53
Autore:
Lomax, M; Fried, M;
Indirizzi:
Imperial Canc Res Fund, London WC2A 3PX, England Imperial Canc Res Fund London England WC2A 3PX London WC2A 3PX, England Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94115 USA Univ Calif San Francisco San Francisco CA USA 94115 ancisco, CA 94115 USA
Titolo Testata:
ONCOGENE
fascicolo: 36, volume: 20, anno: 2001,
pagine: 4951 - 4960
SICI:
0950-9232(20010816)20:36<4951:PVDAST>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR P53; PROTEIN PHOSPHATASE-2A; GENE-PRODUCT; T-ANTIGEN; MDM2; P19(ARF); TRANSFORMATION; CELLS; PHOSPHORYLATION; DEGRADATION;
Keywords:
ARF; MDM2; oncogene co-operation; p53; polyoma virus; polyoma virus T-antigens;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Fried, M Imperial Canc Res Fund, Lincolns Inn Fields,POB 123, London WC2A 3PX, England Imperial Canc Res Fund Lincolns Inn Fields,POB 123 London England WC2A 3PX
Citazione:
M. Lomax e M. Fried, "Polyoma virus disrupts ARF signaling to p53", ONCOGENE, 20(36), 2001, pp. 4951-4960

Abstract

Polyoma virus (Py) differs from other small DNA tumor viruses in not encoding a protein that inactivates p53. The complete Py early region encoding the large T-antigen (PyLT), middle T-antigen (PyMT) and small T-antigen (PyST) will transform primary rodent cells and REF52 cells, but PyMT, the main Py oncogene, by itself will only transform these cells when p53 or ARF is inactivated. We have related Py oncogene cooperation with the effects of thePy T-antigens on the ARF-p53 signaling pathway. PyMT activates an ARF-induced p53-mediated block to cell division explaining the inability of PyMT alone to generate dividing transformed cells. In contrast, in REF52 cells transformed by the whole Py early region (PyREF52), ARF is upregulated but p53is not activated. Thus PyLT and/or PyST negates the PyMT-induced ARF-mediated block to cell division by disrupting the signaling pathway from ARF to p53. Although there is no detectable interaction or co-localization of endogenous ARF (nucleoli) and MDM2 (nucleoplasm) in PyREF52 cells, expression of transfected ectopic ARF results in an MDM2/ARF interaction and sequestration of MDM2 into the nucleoli. Sequestration of MDM2 by ARF in the nucleoliis not essential for a p53 response in REF52 cells as activation of Raf inREF52Raf-ER cells results in an ARF-induced p53-mediated cell cycle block in the absence of a detectable ARF-MDM2 interaction. Py may provide new insights into the cellular ARF-p53 signaling pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:20:59