中国科学院上海有机化学研究所机构知识库
Advanced  
SIOC OpenIR  > 生命有机化学国家重点实验室  > 期刊论文
学科主题: 生命有机化学
题名: Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death
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
作者: 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
通讯作者: 袁钧瑛
刊名: J. Cell Biol.
发表日期: 2015
DOI: 10.1083/jcb.201503044
卷: 210, 期:5, 页:705-716
收录类别: SCI
文章类型: 论文
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.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000360685600006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/39525
Appears in Collections:生命有机化学国家重点实验室_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
2015465.pdf(3915KB)期刊论文作者接受稿开放获取View Download

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

Recommended Citation:
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.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[XIA HONGGUANG]'s Articles
[NAJAFOV AYAZ]'s Articles
[GENG JIEFEI]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[XIA HONGGUANG]‘s Articles
[NAJAFOV AYAZ]‘s Articles
[GENG JIEFEI]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: 2015465.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Powered by CSpace