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Titolo:
p53 Accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101
Autore:
Ruland, J; Sirard, C; Elia, A; MacPherson, D; Wakeham, A; Li, LM; de la Pompa, JL; Cohen, SN; Mak, TW;
Indirizzi:
Amgen Inst, Toronto, ON M5G 2C1, Canada Amgen Inst Toronto ON Canada M5G 2C1 en Inst, Toronto, ON M5G 2C1, Canada Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada Univ TorontoToronto ON Canada M5G 2C1 Inst, Toronto, ON M5G 2C1, Canada Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada Univ Toronto Toronto ON Canada M5G 2C1 ophys, Toronto, ON M5G 2C1, Canada Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada Univ Toronto Toronto ON Canada M5G 2C1 munol, Toronto, ON M5G 2C1, Canada Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 d, Dept Genet, Stanford, CA 94305 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 4, volume: 98, anno: 2001,
pagine: 1859 - 1864
SICI:
0027-8424(20010213)98:4<1859:PADCPA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSCRIPTIONAL ACTIVATION; MDM2-DEFICIENT MICE; TUMOR SUPPRESSION; IN-VIVO; MOUSE; GENE; DELETION; RESCUE; MUTATION; BRCA1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Mak, TW Amgen Inst, 620 Univ Ave, Toronto, ON M5G 2C1, Canada Amgen Inst 620 Univ Ave Toronto ON Canada M5G 2C1 M5G 2C1, Canada
Citazione:
J. Ruland et al., "p53 Accumulation, defective cell proliferation, and early embryonic lethality in mice lacking tsg101", P NAS US, 98(4), 2001, pp. 1859-1864

Abstract

Functional inactivation of the tumor susceptibility gene tsg101 in NIH 3T3fibroblasts results in cellular transformation and the ability to form metastatic: tumors in nude mice. The N-terminal region of tsg101 protein is structurally similar to the catalytic domain of ubiquitin-conjugating enzymes, suggesting a potential role of tsg101 in ubiquitin-mediated protein degradation. The C-terminal domain of TSG101 can function as a repressor of transcription, To investigate the physiological function of tsg101, we generated a null mutation of the mouse gene by gene targeting. Homozygous tsg101-/-embryos fail to develop past day 6.5 of embryogenesis (E6.5), are reduced in size, and do not form mesoderm. Mutant embryos show a decrease in cellular proliferation in vivo and in vitro but no increase in apoptosis, Although levels of p53 transcripts were not affected in tsg101-/- embryos, p53 protein accumulated dramatically, implying altered posttranscriptional controlof p53. In addition, transcription of the p53 effector, cyclin-dependent kinase inhibitor p21(WAF-1/CIP-1), was increased 5-to 10-fold, whereas activation of MDM2 transcription secondary to p53 elevation was not observed. Introduction of a p53 null mutation into tsg101-/- embryos rescued the gastrulation defect and prolonged survival until E8.5. These results demonstrate that tsg101 is essential for the proliferative burst before the onset of gastrulation and establish a functional connection between tsg101 and the p53pathway in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 17:01:34