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Titolo:
The transcription factor E2F1 promotes dopamine-evoked neuronal apoptosis by a mechanism independent of transcriptional activation
Autore:
Hou, ST; Cowan, E; Walker, T; Ohan, N; Dove, M; Rasqinha, I; MacManus, JP;
Indirizzi:
Natl Res Council Canada, Inst Biol Sci, Apoptosis Res Grp, Ottawa, ON K1A 0R6, Canada Natl Res Council Canada Ottawa ON Canada K1A 0R6 tawa, ON K1A 0R6, Canada
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 2, volume: 78, anno: 2001,
pagine: 287 - 297
SICI:
0022-3042(200107)78:2<287:TTFEPD>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACTOR-KAPPA-B; CELL-DEATH; PARKINSONS-DISEASE; POSTMITOTIC NEURONS; SEPARABLE FUNCTIONS; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; FAMILY MEMBER; GENE-TRANSFER; DNA-BINDING;
Keywords:
adenovirus; caspase 3; dopamine; E2F1; neuronal apoptosis; p19(ARF);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Hou, ST Natl Res Council Canada, Inst Biol Sci, Apoptosis Res Grp, Montreal Rd Labs,Bldg M-54, Ottawa, ON K1A 0R6, Canada Natl Res Council Canada Montreal Rd Labs,Bldg M-54 Ottawa ON Canada K1A 0R6
Citazione:
S.T. Hou et al., "The transcription factor E2F1 promotes dopamine-evoked neuronal apoptosis by a mechanism independent of transcriptional activation", J NEUROCHEM, 78(2), 2001, pp. 287-297

Abstract

The E2F1 transcription factor plays an important role in promoting neuronal apoptosis; however, it is not clear how E2F1 does this. Here we show thatE2F1 is involved in dopamine (DA)-evoked apoptosis in cerebellar granule neurons (CGNs), E2F1 -/- CGNs and CGNs expressing an antisense E2F1 cDNA were significantly protected from DA-toxicity relative to controls, The neuronal protection was accompanied by significantly reduced caspase 3 activity. E2F1-mediated neuronal apoptosis did not require activation of gene transcription because: (1) ectopic expression of E2F1 or its mutants lacking the transactivation domain induced neuronal apoptosis, whereas an E2F1 mutant lacking the DNA-binding domain did not; (2) under all of these conditions, known E2F1 target genes including cyclin A, cdc2 and p19(ARF) were not induced; and (3) DA-evoked neuronal apoptosis was associated with up-regulated E2F1, but not transcription of its target genes. Finally, E2F1-mediated neuronal apoptosis was associated with reduced nuclear factor (NF)-kappaB DNA-binding activity. Taken together, these data suggest that E2F1 promotes DA-evoked caspase 3-dependent neuronal apoptosis by a mechanism independent of gene transactivation, and this may possibly occur through inhibition of anti-apoptotic genes including NF-kappaB.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 12:47:03