chaperone proteins induced by heat shock

In TNF signaling, TRADD recruits FADD following formation and release of a TNFR1 complex ( Chinnaiyan et al., 1996 Hsu et al., 1996a Hsu et al., 1996b Micheau and Tschopp, 2003) to initiate pro-caspase-8 activation. Homotypic interaction between the DDs of Fas and FADD induces the recruitment and self-activation of pro-caspase-8 ( Chinnaiyan et al., 1995). Tumor necrosis factor receptor 1 (TNFR1) and the Fas receptors contain death domains (DDs) and recruit the DD-containing adaptor molecules TNFR1-associated death domain (TRADD) and Fas-associated death domain (FADD), respectively. The extrinsic pathway can be initiated by one of several cellsurface death receptors when bound by the appropriate ligand ( Locksley et al., 2001 Screaton and Xu, 2000). This promotes the autoprocessing of pro-caspase-9 ( Srinivasula et al., 1998), which in turn recruits and cleaves pro-caspase-3 that is then released into the cytosol to degrade target substrates proteolytically ( Cain et al., 1999). Once released into the cytosol, cytochrome c binds to an adaptor protein, Apaf-1, which self-oligomerizes and recruits pro-caspase-9 to form the apoptosome complex ( Zou et al., 1997 Zou et al., 1999). The precise mechanism of cytochrome c release remains unclear but is regulated by the antagonistic activities of the Bcl-2 family ( Green and Reed, 1998 Willis et al., 2003). These include cytochrome c ( Kluck et al., 1997 Yang et al., 1997a), Smac/Diablo ( Du et al., 2000 Verhagen et al., 2000), AIF ( Susin et al., 1999), EndoG ( Li et al., 2001) and HtrA2/Omi ( Suzuki et al., 2001). The intrinsic pathway is characterized by the permeabilization of the outer mitochondrial membrane and the release of several pro-apoptotic factors into the cytosol. The sequence of events culminating in the activation of caspases can be broadly categorized into two pathways: the `intrinsic' pathway ( Fig. The coordinated activities of the Hsps thus modulate multiple events within apoptotic pathways to help sustain cell survival following damaging stimuli. Several signaling cascades involved in the regulation of key elements within the apoptotic cascade are also subject to modulation by Hsps, including those involving JNK, NF-κB and AKT. The disruption of apoptosome formation represents another mechanism by which Hsps can prevent caspase activation and induction of apoptosis.

Hsps can inhibit the activity of pro-apoptotic Bcl-2 proteins to prevent permeabilization of the outer mitochondrial membrane and release of apoptogenic factors. Several mechanisms proposed to account for these observations impact on both the `intrinsic', mitochondria-dependent and the `extrinsic', death-receptor-mediated pathways to apoptosis. The underlying ability of Hsps to maintain cell survival correlates with an inhibition of caspase activation and apoptosis that can, but does not always, depend upon their chaperoning activities. Heat shock proteins (Hsps) are a family of highly homologous chaperone proteins that are induced in response to environmental, physical and chemical stresses and that limit the consequences of damage and facilitate cellular recovery.

Chaperone proteins induced by heat shock