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

Park,Yoo Hoi; Seo,Ji Hae; Park,Ji-Hyeon; Lee,Hye Shin; Kim,Kyu-Won

doi:10.3892/ijo.2017.4039

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

Authors:
- Yoo Hoi Park
- Ji Hae Seo
- Ji-Hyeon Park
- Hye Shin Lee
- Kyu-Won Kim
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Affiliations: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea, Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea
Published online on: June 12, 2017 https://doi.org/10.3892/ijo.2017.4039
Pages: 573-578

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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.

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