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. 2020 Mar 2;9(3):587. doi: 10.3390/cells9030587

Figure 5.

Figure 5

HSP70 in apoptotic signaling pathways. (A) HSP70 in intrinsic apoptosis. In TNF-α induced apoptosis, HSP70 inhibits JNK and p38, thus, preventing the translocation of Bax and Bid to the mitochondria [150,156,163]. This blocks the release of cytochrome c to the cytosol and its formation of apoptosome complex with Apaf-1 and caspase-9. HSP70 may also disrupt the formation of apoptosome by binding to Apaf-1, preventing its association with procaspase-9 [164]. In addition, HSP70 stabilizes lysosomal membrane, inhibiting cathepsin release to the cytosol for the activation of intrinsic apoptotic pathway. (B) HSP70 in extrinsic apoptosis. HSP70 interacts with TRAIL-R1 and TRAIL-R2 and prevents the formation of DISC complex required for the initiation of extrinsic apoptosis. JNK, c-Jun N-terminal kinase; Cyt C, cytochrome c; Bax, Bcl-2-associated X protein; Bid, BH3 interacting-domain death agonist; p38, p38 mitogen-activated protein kinase; Apaf-1, apoptotic protease-activating factor 1; ASK, apoptosis signal-regulating kinase 1; TRAIL, TNF-related apoptosis-inducing ligand; TRAIL-R1/R2, TNF-related apoptosis-inducing ligand receptor 1/2; FADD, FAS-associated death domain (FADD).