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Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy
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
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)
2009
发表期刊J. Cell Biol.
ISSN0021-9525
卷号185期号:4页码:629-639
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.
学科领域生命有机化学
部门归属上海药物所; 上海有机所; 哈佛医学院
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收录类别SCI
语种英语
WOS记录号WOS:000266279900009
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被引频次:55[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/15611
专题生命有机化学国家重点实验室
通讯作者Ma DW(马大为); Yuan JY(袁钧英); Yu Q(俞强)
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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.
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