The EMBO Journal advance online publication, 23 August，2013; doi:10.1038/emboj.2013.189
WASH inhibits autophagy through suppression of Beclin 1 ubiquitination
Pengyan Xia1,5, Shuo Wang1,5, Ying Du1, Zhenao Zhao2, Lei Shi1, Lei Sun3, Guanling Huang1, Buqing Ye1, Chong Li1, Zhonghua Dai1, Ning Hou4, Xuan Cheng4, Qingyuan Sun2, Lei Li2, Xiao Yang4,* and Zusen Fan1,*
Abstract
Autophagy degrades cytoplasmic proteins and organelles to recycle cellular components that are required for cell survival and tissue homeostasis. However, it is not clear how autophagy is regulated in mammalian cells. WASH (Wiskott–Aldrich syndrome protein (WASP) and SCAR homologue) plays an essential role in endosomal sorting through facilitating tubule fission via Arp2/3 activation. Here, we demonstrate a novel function of WASH in modulation of autophagy. We show that WASH deficiency causes early embryonic lethality and extensive autophagy of mouse embryos.WASH inhibits vacuolar protein sorting (Vps)34 kinase activity and autophagy induction. We identified that WASH is a new interactor of Beclin 1. Beclin 1 is ubiquitinated at lysine 437 through lysine 63 linkage in cells undergoing autophagy. Ambra1 is an E3 ligase for lysine 63-linked ubiquitination of Beclin 1 that is required for starvation-induced autophagy. The lysine 437 ubiquitination of Beclin 1 enhances the association with Vps34 to promote Vps34 activity. WASH can suppress Beclin 1 ubiquitination to inactivate Vps34 activity leading to suppression of autophagy.
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201308/t20130826_3918146.html
文章链接：http://www.nature.com/emboj/journal/vaop/ncurrent/pdf/emboj2013189a.pdf
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