Hsp27 negatively regulates cell death by interacting with cytochrome c.
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.
Bruey
J M
JM
INSERM U-517, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France.
Ducasse
C
C
Bonniaud
P
P
Ravagnan
L
L
Susin
S A
SA
Diaz-Latoud
C
C
Gurbuxani
S
S
Arrigo
A P
AP
Kroemer
G
G
Solary
E
E
Garrido
C
C
D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation; D005420:Flavoproteins / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D003574:Cytochrome c Group; D005420:Flavoproteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D020169:Caspases