Figure 3

Modulation of the extrinsic and intrinsic apoptotic signaling cascades by HSPs. HSP 27, 72, and 90 inhibit JNK activation through suppression of ASK-1 and SEK Kinase. HSP 27, 60, 72, and 90 can prevent Bid and Bax translocation to the mitochondria. Once mitochondrial permeability is compromised, αβ crystallin, HSP 27, 72, and 90 can prevent apoptosis by binding released cytochrome c and by preventing Apaf-1 oligomerization and recruitment of pro-caspase-9 for apoptosome formation. HSP 60 has both anti- and pro-apoptotic properties, binding Bax in the cytosol and accelerating maturation of caspase-3. Dashed lines indicate inhibitory effects.