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Kwon, Hyug Moo
Immunometabolism and Cancer Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorder, Genomic instability

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TonEBP Promotes beta-Cell Survival under ER Stress by Enhancing Autophagy

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Title
TonEBP Promotes beta-Cell Survival under ER Stress by Enhancing Autophagy
Author
Kang, Hyun JeYoo, Eun JinLee, Hwan HeeAn, Seung MinPark, HyunLee-Kwon, WhaseonChoi, Soo YounKwon, Hyug Moo
Issue Date
2020-09
Publisher
MDPI
Citation
CELLS, v.9, no.9
Abstract
The endoplasmic reticulum (ER) stress response and autophagy are important cellular responses that determine cell fate and whose dysregulation is implicated in the perturbation of homeostasis and diseases. Tonicity-responsive enhancer-binding protein (TonEBP, also called NFAT5) is a pleiotropic stress protein that mediates both protective and pathological cellular responses. Here, we examined the role of TonEBP in beta-cell survival under ER stress. We found that TonEBP increases beta-cell survival under ER stress by enhancing autophagy. The level of TonEBP protein increased under ER stress due to a reduction in its degradation via the ubiquitin-proteasome pathway. In response to ER stress, TonEBP increased autophagosome formations and suppressed the accumulation of protein aggregates and beta-cell death. The Rel-homology domain of TonEBP interacted with FIP200, which is essential for the initiation of autophagy, and was required for autophagy and cell survival upon exposure to ER stress. Mice in whichTonEBPwas specifically deleted in pancreatic endocrine progenitor cells exhibited defective glucose homeostasis and a loss of islet mass. Taken together, these findings demonstrate that TonEBP protects against ER stress-induced beta-cell death by enhancing autophagy.
URI
https://scholarworks.unist.ac.kr/handle/201301/48743
URL
https://www.mdpi.com/2073-4409/9/9/1928
DOI
10.3390/cells9091928
ISSN
2073-4409
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BIO_Journal Papers
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