作者
Daolin Tang, Rui Kang, Kristen M Livesey, Chun-Wei Cheh, Adam Farkas, Patricia Loughran, George Hoppe, Marco E Bianchi, Kevin J Tracey, Herbert J Zeh III, Michael T Lotze
发表日期
2010/9/6
期刊
Journal of Cell Biology
卷号
190
期号
5
页码范围
881-892
出版商
The Rockefeller University Press
简介
Autophagy clears long-lived proteins and dysfunctional organelles and generates substrates for adenosine triphosphate production during periods of starvation and other types of cellular stress. Here we show that high mobility group box 1 (HMGB1), a chromatin-associated nuclear protein and extracellular damage-associated molecular pattern molecule, is a critical regulator of autophagy. Stimuli that enhance reactive oxygen species promote cytosolic translocation of HMGB1 and thereby enhance autophagic flux. HMGB1 directly interacts with the autophagy protein Beclin1 displacing Bcl-2. Mutation of cysteine 106 (C106), but not the vicinal C23 and C45, of HMGB1 promotes cytosolic localization and sustained autophagy. Pharmacological inhibition of HMGB1 cytoplasmic translocation by agents such as ethyl pyruvate limits starvation-induced autophagy. Moreover, the intramolecular disulfide bridge (C23/45) of …
引用总数
2011201220132014201520162017201820192020202120222023202438667793799071778282109787025
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