HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery

Hyun Wook Ryu, Hye Rim Won, Dong Hoon Lee, So Hee Kwon

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Histone deacetylase 6 (HDAC6) plays an important role in stress responses such as misfolded protein-induced aggresomes, autophagy, and stress granules. However, precisely how HDAC6 manages response during and after cellular stress remains largely unknown. This study aimed to investigate the effect of HDAC6 on various stress and post-stress recovery responses. We showed that HIF-1α protein levels were reduced in HDAC6 knockout (KO) MEFs compared to wild-type (WT) MEFs in hypoxia. Furthermore, under hypoxia, HIF-1α levels were also reduced following rescue with either a catalytically inactive or a ubiqiutin-binding mutant HDAC6. HDAC6 deacetylated and upregulated the stability of HIF-1α, leading to activation of HIF-1α function under hypoxia. Notably, both the deacetylase and ubiquitin-binding activities of HDAC6 contributed to HIF-1α stabilization, but only deacetylase activity was required for HIF-1α transcriptional activity. Suppression of HDAC6 enhanced the interaction between HIF-1α and HSP70 under hypoxic conditions. In addition to hypoxia, depletion of HDAC6 caused hypersensitivity to cell death during oxidative stress and post-stress recovery. However, HDAC6 depletion had no effect on cell death in response to heat shock or ionizing radiation. Overall, our data suggest that HDAC6 may serve as a critical stress regulator in response to different cellular stresses.

Original languageEnglish
Pages (from-to)253-261
Number of pages9
JournalCell Stress and Chaperones
Volume22
Issue number2
DOIs
Publication statusPublished - 2017 Mar 1

Fingerprint

Histone Deacetylases
Cell death
Cell Death
Recovery
Heat-Shock Response
Oxidative stress
Ionizing radiation
Autophagy
Ubiquitin
Ionizing Radiation
Hypersensitivity
Proteins
Oxidative Stress
Stabilization
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

Ryu, Hyun Wook ; Won, Hye Rim ; Lee, Dong Hoon ; Kwon, So Hee. / HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery. In: Cell Stress and Chaperones. 2017 ; Vol. 22, No. 2. pp. 253-261.
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HDAC6 regulates sensitivity to cell death in response to stress and post-stress recovery. / Ryu, Hyun Wook; Won, Hye Rim; Lee, Dong Hoon; Kwon, So Hee.

In: Cell Stress and Chaperones, Vol. 22, No. 2, 01.03.2017, p. 253-261.

Research output: Contribution to journalArticle

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