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Titolo:
Heat-shock protein 70 antagonizes apoptosis-inducing factor
Autore:
Ravagnan, L; Gurbuxani, S; Susin, SA; Maisse, C; Daugas, E; Zamzami, N; Mak, T; Jaattela, M; Penninger, JM; Garrido, C; Kroemer, G;
Indirizzi:
Fac Med & Pharm Dijon, INSERM U517, F-21033 Dijon, France Fac Med & Pharm Dijon Dijon France F-21033 M U517, F-21033 Dijon, France Inst Gustave Roussy, CNRS UMR 1599, F-94805 Villejuif, France Inst GustaveRoussy Villejuif France F-94805 , F-94805 Villejuif, France Hop Tenon, Serv Nephrol B, Hop Paris, Assistance Publ, F-75020 Paris, France Hop Tenon Paris France F-75020 s, Assistance Publ, F-75020 Paris, France Univ Toronto, Dept Med Biophys & Immunol, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada Univ Toronto Toronto ON Canada M5G 2C1 Inst, Toronto, ON M5G 2C1, Canada Univ Toronto, Amgen Inst, Toronto, ON M5G 2C1, Canada Univ Toronto Toronto ON Canada M5G 2C1 Inst, Toronto, ON M5G 2C1, Canada Danish Canc Soc, Inst Canc Biol, Apoptosis Lab, DK-2100 Copenhagen, Denmark Danish Canc Soc Copenhagen Denmark DK-2100 , DK-2100 Copenhagen, Denmark
Titolo Testata:
NATURE CELL BIOLOGY
fascicolo: 9, volume: 3, anno: 2001,
pagine: 839 - 843
SICI:
1465-7392(200109)3:9<839:HP7AAF>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-DEATH; APAF-1 APOPTOSOME; HUMAN HSP70; IN-VIVO; HEAT-SHOCK-PROTEIN-70; BCL-2; MITOCHONDRIA; CASPASES; PATHWAYS; COMPLEX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Garrido, C Fac Med & Pharm Dijon, INSERM U517, 7 Blvd Jeanne dArc, F-21033Dijon, France Fac Med & Pharm Dijon 7 Blvd Jeanne dArc Dijon France F-21033
Citazione:
L. Ravagnan et al., "Heat-shock protein 70 antagonizes apoptosis-inducing factor", NAT CELL BI, 3(9), 2001, pp. 839-843

Abstract

Heat-shock protein 70 (Hsp70) has been reported to block apoptosis by binding apoptosis protease activating factor-1 (Apaf-1), thereby preventing constitution of the apoptosome, the Apaf-1/cytochrome c/caspase-9 activation complex(1,2). Here we show that overexpression of Hsp70 protects Apaf-1(-/-)cells against death induced by serum withdrawal, indicating that Apaf-1 isnot the only target of the anti-apoptotic action of Hsp70. We investigatedthe effect of Hsp70 on apoptosis mediated by the caspase-independent deatheffector apoptosis inducing factor (AlF), which is a mitochondrial intermembrane flavoprotein(3,4). In a cell-free system, Hsp70 prevented the AIF-induced chromatin condensation of purified nuclei. Hsp70 specifically interacted with AlF, as shown by ligand blots and co-immunoprecipitation. Cells overexpressing Hsp70 were protected against the apoptogenic effects of AIF targeted to the extramitochondrial compartment. In contrast, an anti-sense Hsp70 complementary DNA, which reduced the expression of endogenous Hsp70, increased sensitivity to the lethal effect of AIR The ATP-binding domain of Hsp70 seemed to be dispensable for inhibiting cell death induced by serum withdrawal, AIF binding and AIF inhibition, although it was required for Apaf-1 binding. Together, our data indicate that Hsp70 can inhibit apoptosis byinterfering with target proteins other than Apaf-1, one of which is AIR

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 14:20:25