Hsp70 acetylation prevents caspase-dependent/independent apoptosis and autophagic cell death in cancer cells

Abstract

Cancer cells are continuously challenged by adverse environmental factors including hypoxia, metabolite restriction, and immune reactions, and must adopt diverse strategies to survive. Heat shock protein (Hsp) 70 plays a central role in protection against stress-induced cell death by maintaining protein homeostasis and interfering with the process of programmed cell death. Recent findings have suggested that Hsp70 acetylation is a key regulatory modification required for its chaperone activity, but its relevance in the process of programmed cell death and the underlying mechanisms involved are not well understood. In this study, we sought to investigate mechanisms mediated by Hsp70 acetylation in relation to apoptotic and autophagic programmed cell death. Upon stress-induced apoptosis, Hsp70 acetylation inhibits apoptotic cell death, mediated by Hsp70 association with apoptotic protease-activating factor (Apaf)-1 and apoptosis-inducing factor (AIF), key modulators of caspase-dependent and -independent apoptotic pathways, respectively. Hsp70 acetylation also attenuated autophagic cell death associated with upregulation of autophagy-related genes and autophagosome induction. Collectively, these results suggest that the acetylation of Hsp70 plays key regulatory roles in cell death pathways as well as in its function as a chaperone, together enabling cellular protection in response to stress.

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems

“…Our findings suggested that EFEN treatment up-regulated CDC2/cyclin B levels and further induced G2/M arrest and that EFEN induced apoptosis by up-regulating Bcl-2/Bax ration and activating caspase-3, -8 and -9. Thus, EFEN induced apoptosis through diverse caspase-dependent pathways (Park et al., 2017 ). More work should be done to classify in more detail the apoptotic pathways involved.…”

Promoting TTC4 and HSP70 interaction and translocation of annexin A7 to lysosome inhibits apoptosis in vascular endothelial cells

“…As we all known, HSP70 was a member of heat shock protein molecular chaperone family. 45,46 HSP70 played a central role in protection against stress-induced cell death. Therefore, we further studied the effect of HSP70 on apoptosis.…”

Cellular and epigenetic changes induced by heat stress in bovine preimplantation embryos

“…This indicates a role of HSF1 in histone acetylation control during heat stress. HSP70 acetylation can also protect stressed cells inhibiting cell death through association with apoptotic protease‐activating factor (APAF)‐1 (Caspase‐dependent cell death) and apoptosis‐inducing factor (AIF; caspase‐independent cell death; Candé et al, ; Y. H. Park, Seo, Park, Lee, & Kim, ; Ravagnan et al, ; Saleh, Srinivasula, Balkir, Robbins, & Alnemri, ). The balance between protein refolding and degradation in response to stress is regulated by acetyltransferase arrest defective 1 mediated HSP70 acetylation (Seo et al, ).…”