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A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis | |
2015 | |
发表期刊 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
ISSN | 0027-8424 |
卷号 | 112期号:16页码:5017-5022 |
发表状态 | 已发表 |
DOI | 10.1073/pnas.1505244112 |
摘要 | Receptor-interacting protein kinase 3, RIP3, and a pseudokinase mixed lineage kinase-domain like protein, MLKL, constitute the core components of the necroptosis pathway, which causes programmed necrotic death in mammalian cells. Latent RIP3 in the cytosol is activated by several upstream signals including the related kinase RIP1, which transduces signals from the tumor necrosis factor (TNF) family of cytokines. We report here that RIP3 activation following the induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone complex. This complex physically associates with RIP3. Chemical inhibitors of HSP90 efficiently block necroptosis by preventing RIP3 activation. Cells with knocked down CDC37 were unable to respond to necroptosis stimuli. Moreover, an HSP90 inhibitor that is currently under clinical development as a cancer therapy was able to prevent systemic inflammatory response syndrome in rats treated with TNF-alpha. HSP90 and CDC37 cochaperone complex-mediated protein folding is thus an important part of the RIP3 activation process during necroptosis. |
关键词 | HSP90 CDC37 RIP3 necrosis kinase |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000353239100056 |
WOS关键词 | MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; PROGRAMMED NECROSIS ; CELL-DEATH ; TNF-ALPHA ; MLKL ; HSP90 ; PHOSPHORYLATION ; DISRUPTION ; APOPTOSIS |
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/120048 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Wang, Xiaodong; Shen, Zhirong |
作者单位 | 1.Beijing Normal Univ, Grad Program, Beijing 100875, Peoples R China 2.Natl Inst Biol Sci, Beijing 102206, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Collaborat Innovat Ctr Syst Biomed, Shanghai 200240, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Dianrong,Xu, Tao,Cao, Yang,et al. A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(16):5017-5022. |
APA | Li, Dianrong.,Xu, Tao.,Cao, Yang.,Wang, Huayi.,Li, Lin.,...&Shen, Zhirong.(2015).A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(16),5017-5022. |
MLA | Li, Dianrong,et al."A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.16(2015):5017-5022. |
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