2. Academic Validation
  3. ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation

ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation

  • Nat Commun. 2016 Oct 6;7:12882. doi: 10.1038/ncomms12882.
Ji Hae Seo 1,  Ji-Hyeon Park 1,  Eun Ji Lee 1,  Tam Thuy Lu Vo 1,  Hoon Choi 1,  Jun Yong Kim 2,  Jae Kyung Jang 1,  Hee-Jun Wee 1,  Hye Shin Lee 1,  Se Hwan Jang 3,  Zee Yong Park 3,  Jaeho Jeong 4,  Kong-Joo Lee 4,  Seung-Hyeon Seok 5,  Jin Young Park 5,  Bong Jin Lee 5,  Mi-Ni Lee 6,  Goo Taeg Oh 6,  Kyu-Won Kim 1 2 7
Affiliations

Affiliations

  • 1 SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
  • 2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
  • 3 School of Life Sciences, Gwangju Institute of Science &Technology, Gwangju 61005, Korea.
  • 4 Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea.
  • 5 The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
  • 6 Department of Life Sciences, Ewha Womans University, Seoul 03760, Korea.
  • 7 Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang 25354, Korea.
PMID: 27708256 DOI: 10.1038/ncomms12882
Abstract

Heat shock protein (HSP)70 is a molecular chaperone that maintains protein homoeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. However, the mechanisms by which HSP70 balances these opposing functions under stress conditions remain unknown. Here, we demonstrate that HSP70 preferentially facilitates protein refolding after stress, gradually switching to protein degradation via a mechanism dependent on ARD1-mediated HSP70 acetylation. During the early stress response, HSP70 is immediately acetylated by ARD1 at K77, and the acetylated HSP70 binds to the co-chaperone Hop to allow protein refolding. Thereafter, HSP70 is deacetylated and binds to the ubiquitin ligase protein CHIP to complete protein degradation during later stages. This switch is required for the maintenance of protein homoeostasis and ultimately rescues cells from stress-induced cell death in vitro and in vivo. Therefore, ARD1-mediated HSP70 acetylation is a regulatory mechanism that temporally balances protein refolding/degradation in response to stress.

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