Hsp27 negatively regulates cell death by interacting with cytochrome c

• Published in: Nature cell biology Vol. 2; no. 9; pp. 645 - 652
• Main Authors: Garrido, Carmen, Bruey, Jean-Marie, Ducasse, Cécile, Bonniaud, Philippe, Ravagnan, Luigi, Susin, Santos A, Diaz-Latoud, Chantal, Gurbuxani, Sandeep, Arrigo, André-Patrick, Kroemer, Guido, Solary, Eric
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2000
• Subjects: Apoptosis; Apoptosis Inducing Factor; Caspases - metabolism; Cell death; Cell interaction; Cytochrome; Cytochrome c; Cytochrome c Group - metabolism; Cytosol - metabolism; Cytosol - physiology; Enzyme Activation; Flavoproteins - metabolism; Heat-Shock Proteins - metabolism; HSP27 Heat-Shock Proteins; Humans; Mammals; Membrane Proteins - metabolism; Mitochondria; Molecular chaperones; Mortality; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Physiological aspects; Proteins; U937 Cells
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/35023595

Mammalian cells respond to stress by accumulating or activating a set of highly conserved proteins known as heat-shock proteins (HSPs). Several of these proteins interfere negatively with apoptosis. We show that the small HSP known as Hsp27 inhibits cytochrome-c-mediated activation of caspases in the cytosol. Hsp27 does not interfere with granzyme-B-induced activation of caspases, nor with apoptosis-inducing factor-mediated, caspase-independent, nuclear changes. Hsp27 binds to cytochrome c released from the mitochondria to the cytosol and prevents cytochrome-c-mediated interaction of Apaf-1 with procaspase-9. Thus, Hsp27 interferes specifically with the mitochondrial pathway of caspase-dependent cell death.