Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome

The cellular-stress response can mediate cellular protection through expres sion of heat-shock protein (Hsp) 70, which can interfere with the process o f apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteas es. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 olig omers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitm ent of caspases to the apoptosome complex. Hsp70 therefore suppresses apopt osis by directly associating with Apaf-1 and blocking the assembly of a fun ctional apoptosome.