作者
Aditi U Gurkar, Kiki Chu, Lakshmi Raj, Richard Bouley, Seung-Hwan Lee, Young-Bum Kim, Sandra E Dunn, Anna Mandinova, Sam W Lee
发表日期
2013/7/23
期刊
Nature communications
卷号
4
期号
1
页码范围
1-13
出版商
Nature Publishing Group
简介
The Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of cellular activities, including those involved in tumour metastasis and apoptosis. Here we identify an indispensable function of ROCK1 in metabolic stress-induced autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal component of the phosphoinositide 3-kinase class III lipid–kinase complex that induces autophagy, as an interacting partner of ROCK1. Upon nutrient deprivation, activated ROCK1 promotes autophagy by binding and phosphorylating Beclin1 at Thr119. This results in the specific dissociation of the Beclin1–Bcl-2 complex without affecting the Beclin1–UVRAG interaction. Conversely, inhibition of ROCK1 activity increases Beclin1–Bcl-2 association, thus reducing nutritional stress-mediated autophagy. Genetic knockout of ROCK1 function in mice also leads to impaired autophagy as evidenced …
引用总数
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