Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades
2018
发表期刊MOLECULAR CANCER RESEARCH
ISSN1541-7786
EISSN1557-3125
卷号16期号:1页码:58-68
发表状态已发表
DOI10.1158/1541-7786.MCR-17-0408
摘要

Hsp70 is a molecular chaperone that binds to "client" proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chemical inhibitors, we found that many of the well-known clients of the related chaperone, Hsp90, are not strikingly responsive to Hsp70 inhibition. Rather, Hsp70 appeared to be important for the stability of the RIP1 (RIPK1) regulators: cIAP1/2 (BIRC1 and BIRC3), XIAP, and cFLIPS/L (CFLAR). These results suggest that Hsp70 limits apoptosis and necroptosis pathways downstream of RIP1. Consistent with this model, MDA-MB-231 breast cancer cells treated with Hsp70 inhibitors underwent apoptosis, while cotreatment with zVAD. fmk switched the cell death pathway to necroptosis. In addition, cell death in response to Hsp70 inhibitors was strongly suppressed by RIP1 knockdown or inhibitors. Thus, these data indicate that Hsp70 plays a previously unrecognized and important role in suppressing RIP1 activity. 68. (C) 2017 AACR.

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收录类别SCI
WOS研究方向Oncology ; Cell Biology
WOS类目Oncology ; Cell Biology
WOS记录号WOS:000419147200005
WOS关键词HEAT-SHOCK-PROTEIN ; SMALL-MOLECULE MODULATORS ; HSP90 FUNCTION ; CELL-DEATH ; CANCER-CELLS ; RIP1 KINASE ; CHAPERONES ; DEGRADATION ; INHIBITOR ; NECROSIS
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120161
专题个人在本单位外知识产出
通讯作者Gestwicki, Jason E.
作者单位
1.Univ Michigan, Program Chem Biol, Ann Arbor, MI 48109 USA
2.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA
3.Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA
4.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
5.Baylor Coll Med, Sect Hematol & Oncol, Dept Med, Baylor Scott & White Res Inst, Dallas, TX USA
推荐引用方式
GB/T 7714
Srinivasan, Sharan R.,Cesa, Laura C.,Li, Xiaokai,et al. Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades[J]. MOLECULAR CANCER RESEARCH,2018,16(1):58-68.
APA Srinivasan, Sharan R..,Cesa, Laura C..,Li, Xiaokai.,Julien, Olivier.,Zhuang, Min.,...&Gestwicki, Jason E..(2018).Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades.MOLECULAR CANCER RESEARCH,16(1),58-68.
MLA Srinivasan, Sharan R.,et al."Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades".MOLECULAR CANCER RESEARCH 16.1(2018):58-68.
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