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Titolo:
Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 andactivation of procaspase-9 by heat shock protein 90
Autore:
Pandey, P; Saleh, A; Nakazawa, A; Kumar, S; Srinivasula, SM; Kumar, V; Weichselbaum, R; Nalin, C; Alnemri, ES; Kufe, D; Kharbanda, S;
Indirizzi:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA HarvardUniv Boston MA USA 02115 a Farber Canc Inst, Boston, MA 02115 USA Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA ThomasJefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 & Cellular Oncol, Chicago, IL 60637 USA Novartis Pharmaceut Corp, Oncol Res, E Hanover, NJ 07936 USA Novartis Pharmaceut Corp E Hanover NJ USA 07936 , E Hanover, NJ 07936 USA
Titolo Testata:
EMBO JOURNAL
fascicolo: 16, volume: 19, anno: 2000,
pagine: 4310 - 4322
SICI:
0261-4189(20000815)19:16<4310:NROCCO>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
WD-40 REPEAT REGION; ICE-LIKE PROTEASE; INDUCED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; PROTEOLYTIC ACTIVATION; MOLECULAR CHAPERONES; ICE/CED-3 PROTEASE; CASPASE ACTIVATION; TYROSINE KINASE; TUMOR-CELLS;
Keywords:
Apaf-1; apoptosis; caspase-9; cytochrome c; Hsp90;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Kharbanda, S Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA Harvard Univ 44 Binney St Boston MA USA 02115 n, MA 02115 USA
Citazione:
P. Pandey et al., "Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 andactivation of procaspase-9 by heat shock protein 90", EMBO J, 19(16), 2000, pp. 4310-4322

Abstract

The release of cytochrome c from mitochondria results in the formation of an Apaf-1-caspase-9 apoptosome and induces the apoptotic protease cascade by activation of procaspase-3. The present studies demonstrate that heat shock protein 90 (Hsp90) forms a cytosolic complex with Apaf-1 and thereby inhibits the formation of the active complex. Immunodepletion of Hsp90 depletes Apaf-1 and thereby inhibits cytochrome c-mediated activation of caspase-9. Addition of purified Apaf-1 to Hsp90-depleted cytosolic extracts restorescytochrome c-mediated activation of procaspase-9. We also show that Hsp90 inhibits cytochrome c-mediated oligomerization of Apaf-1 and thereby activation of procaspase-9. Furthermore, treatment of cells with diverse DNA-damaging agents dissociates the Hsp90-Apaf-1 complex and relieves the inhibition of procaspase-9 activation. These findings provide the first evidence fora negative cytosolic regulator of cytochrome c-dependent apoptosis and forinvolvement of a chaperone in the caspase cascade.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 15:23:30