Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy

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	Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy
	Shen, Shensi ; Zhang PT(张澎涛) ; Lovchik, Martin A. ; Li, Ying ; Tang, Liuya ; Chen, Zhimin ; Zeng, Rong ; Ma DW(马大为) ; Yuan JY(袁钧英) ; Yu Q(俞强)
刊名	J. Cell Biol.
	2009
卷号	185 期号:4 页码:629-639
ISSN号	0021-9525
其他题名	环酯肽毒素通过分子伴侣介导的自吞噬作用促进Hsp90事件蛋白降解
通讯作者	马大为 ; 袁钧英 ; 俞强
英文摘要	Promoting the degradation of Hsp90 client proteins by inhibiting Hsp90, an important protein chaperone, has been shown to be a promising new anticancer strategy. In this study, we show that an oxazoline analogue of apratoxin A (oz-apraA), a cyclodepsipeptide isolated from a marine cyanobacterium, promotes the degradation of Hsp90 clients through chaperone-mediated autophagy (CMA). We identify a KFERQ-like motif as a conserved pentapeptide sequence in the kinase domain of epidermal growth factor receptor (EGFR) necessary for recognition as a CMA substrate. Mutation of this motif prevents EGFR degradation by CMA and promotes the degradation of EGFR through the proteasomal pathway in oz-apraA-treated cells. Oz-apraA binds to Hsc70/Hsp70. We propose that apratoxin A inhibits Hsp90 function by stabilizing the interaction of Hsp90 client proteins with Hsc70/Hsp70 and thus prevents their interactions with Hsp90. Our study provides the first examples for the ability of CMA to mediate degradation of membrane receptors and cross talks of CMA and proteasomal degradation mechanisms.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1083/jcb.200810183
语种	英语
WOS记录号	WOS:000266279900009
公开日期	2013-02-19
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/15611]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	Shen, Shensi,Zhang PT,Lovchik, Martin A.,et al. Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy[J]. J. Cell Biol.,2009,185(4):629-639.
APA	Shen, Shensi.,张澎涛.,Lovchik, Martin A..,Li, Ying.,Tang, Liuya.,...&俞强.(2009).Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy.J. Cell Biol.,185(4),629-639.
MLA	Shen, Shensi,et al."Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy".J. Cell Biol. 185.4(2009):629-639.