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Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death
Alternative Title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
XIA HONGGUANG1; NAJAFOV AYAZ1; GENG JIEFEI1; GALANACOSTA LORENA1; HAN XUEMEI1; GUO YUAN1; SHAN BING1; ZHANG YAOYANG1; NORBERG ERIK1; ZHANG TAO1; PAN LIFENG1; LIU JUNLI1; COLOFF JONATHAN L1; OFENGEIM DIMITRY1; ZHU HONG1; WU KEJIA1; CAI YU1; YATES JOHN R1; ZHU ZHENGJIANG1; Yuan JY(袁钧瑛)1; VAKIFAHMETOGLUNORBERG HELIN1
2015
Source PublicationJ. Cell Biol.
Volume210Issue:5Pages:705-716
AbstractHexokinase 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.
Subtype论文
Subject Area生命有机化学
DOI10.1083/jcb.201503044
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000360685600006
Citation statistics
Cited Times:31[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/39525
Collection生命有机化学国家重点实验室
Corresponding AuthorYuan JY(袁钧瑛)
Affiliation1.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
Recommended Citation
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.
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