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Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of keap1 and prevent oxidative liver damage

Title
Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of keap1 and prevent oxidative liver damage
Authors
Bae S.H.Sung S.H.Oh S.Y.Lim J.M.Lee S.K.Park Y.N.Lee H.E.Kang D.Rhee S.G.
Ewha Authors
이서구배수한강동민
SCOPUS Author ID
이서구scopusscopus; 강동민scopus
Issue Date
2013
Journal Title
Cell Metabolism
ISSN
1550-4131JCR Link
Citation
vol. 17, no. 1, pp. 73 - 84
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2013 Elsevier Inc.
DOI
10.1016/j.cmet.2012.12.002
Appears in Collections:
일반대학원 > 생명·약학부 > Journal papers
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