114 152

Cited 179 times in

Sestrins Activate Nrf2 by Promoting p62-Dependent Autophagic Degradation of Keap1 and Prevent Oxidative Liver Damage

Authors
 Soo Han Bae  ;  Su Haeng Sung  ;  Sue Young Oh  ;  Jung Mi Lim  ;  Se Kyoung Lee  ;  Young Nyun Park  ;  Hye Eun Lee  ;  Dongmin Kang  ;  Sue Goo Rhee 
Citation
 Cell Metabolism, Vol.17(1) : 73-84, 2013 
Journal Title
 Cell Metabolism 
ISSN
 1550-4131 
Issue Date
2013
MeSH
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Autophagy ; Carrier Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cytoskeletal Proteins/metabolism* ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; Kelch-Like ECH-Associated Protein 1 ; Liver/metabolism* ; Liver/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Nuclear Proteins ; Oxidative Stress ; Protein Binding ; Proteins/metabolism* ; Transcription Factors/metabolism* ; Transfection ; Up-Regulation
Keywords
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Autophagy ; Carrier Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Cytoskeletal Proteins/metabolism* ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; Kelch-Like ECH-Associated Protein 1 ; Liver/metabolism* ; Liver/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Nuclear Proteins ; Oxidative Stress ; Protein Binding ; Proteins/metabolism* ; Transcription Factors/metabolism* ; Transfection ; Up-Regulation
Abstract
Sestrins (Sesns) protect cells from oxidative stress. The mechanism underlying the antioxidant effect of Sesns has remained unknown, however. The Nrf2-Keap1 pathway provides cellular defense against oxidative stress by controlling the expression of antioxidant enzymes. We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the antioxidant function of Sesns is mediated through activation of Nrf2 in a manner reliant on p62-dependent autophagic degradation of Keap1. Sesn2 was upregulated in the liver of mice subjected to fasting or subsequent refeeding with a high-carbohydrate, fat-free diet, whereas only refeeding promoted Keap1 degradation and Nrf2 activation, because only refeeding induced p62 expression. Ablation of Sesn2 blocked Keap1 degradation and Nrf2 activation induced by refeeding and thereby increased the susceptibility of the liver to oxidative damage resulting from the acute stimulation of lipogenesis associated with refeeding.
Files in This Item:
T201305659.pdf Download
DOI
10.1016/j.cmet.2012.12.002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
Sung, Su Haeng(성수행)
Rhee, Sue Goo(이서구)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89166
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse