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Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death

文献类型：期刊论文

作者XIA HONGGUANG1; NAJAFOV AYAZ1; GENG JIEFEI1; GALANACOSTA LORENA1; HAN XUEMEI1; GUO YUAN1; SHAN BING1; ZHANG YAOYANG1; NORBERG ERIK1; ZHANG TAO1
刊名J. Cell Biol.
出版日期2015
卷号210期号:5页码:705-716
其他题名分子伴侣介导的自噬降解HK2蛋白会引起细胞代谢灾难和细胞死亡
通讯作者袁钧瑛
英文摘要Hexokinase II (HK2), a key enzyme involved in glucose metabolism, is regulated by growth factor signaling and is required for initiation and maintenance of tumors. Here we show that metabolic stress triggered by perturbation of receptor tyrosine kinase FLT3 in non-acute myeloid leukemia cells sensitizes cancer cells to autophagy inhibition and leads to excessive activation of chaperone-mediated autophagy (CMA). Our data demonstrate that FLT3 is an important sensor of cellular nutritional state and elucidate the role and molecular mechanism of CMA in metabolic regulation and mediating cancer cell death. Importantly, our proteome analysis revealed that HK2 is a CMA substrate and that its degradation by CMA is regulated by glucose availability. We reveal a new mechanism by which excessive activation of CMA may be exploited pharmacologically to eliminate cancer cells by inhibiting both FLT3 and autophagy. Our study delineates a novel pharmacological strategy to promote the degradation of HK2 in cancer cells.
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.201503044
语种英语
WOS记录号WOS:000360685600006
源URL[http://ir.sioc.ac.cn/handle/331003/39525]  
专题上海有机化学研究所_生命有机化学国家重点实验室
作者单位1.美国哈佛大学
2.瑞典卡罗林斯卡学院
3.美国斯克利普斯研究所
4.中科院上海有机化学研究所, 生物与化学交叉研究中心
推荐引用方式
GB/T 7714		 XIA HONGGUANG,NAJAFOV AYAZ,GENG JIEFEI,et al. Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death[J]. J. Cell Biol.,2015,210(5):705-716.
APA XIA HONGGUANG.,NAJAFOV AYAZ.,GENG JIEFEI.,GALANACOSTA LORENA.,HAN XUEMEI.,...&VAKIFAHMETOGLUNORBERG HELIN.(2015).Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death.J. Cell Biol.,210(5),705-716.
MLA XIA HONGGUANG,et al."Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death".J. Cell Biol. 210.5(2015):705-716.

入库方式： OAI收割

来源：上海有机化学研究所

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