| RRC ID |
30497
|
| 著者 |
Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG.
|
| タイトル |
Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage.
|
| ジャーナル |
Cell Metab
|
| 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.
|
| 巻・号 |
17(1)
|
| ページ |
73-84
|
| 公開日 |
2013-1-8
|
| DOI |
10.1016/j.cmet.2012.12.002
|
| PII |
S1550-4131(12)00493-7
|
| PMID |
23274085
|
| 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
Peroxidases
Protein Binding
Proteins / metabolism*
Transcription Factor TFIIH
Transcription Factors / metabolism*
Transfection
Up-Regulation
|
| IF |
21.567
|
| 引用数 |
223
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01390 |
