Hsp27 negatively regulates cell death by interacting with cytochrome c

Mammalian cells respond to stress by accumulating or activating a set of hi ghly conserved proteins known as heat-shock proteins (HSPs), Several of the se proteins interfere negatively with apoptosis, We show that the small HSP known as Hsp27 inhibits cytochrome-c-mediated activation of caspases in th e cytosol, Hsp27 does not interfere with granzyme-B-induced activation of c aspases, 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 wi th procaspase-9, Thus, Hsp27 interferes specifically with the mitochondrial pathway of caspase-dependent cell death.