Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis

doi:10.1016/j.chembiol.2015.08.018

	Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis
	Wang, Lei 3; Li, Dianrong 2,3; Li, Chao 1,4; Li, Lin 3; Chen, She 3; Li, Qiang 3; Wang, Xiaodong 3,5; Lei, Xiaoguang 1,3,4; Shen, Zhirong 3,5
刊名	Cell Chemical Biology
	2016-02-18
卷号	23 期号:2 页码:257-266
ISSN号	2451-9448
DOI	10.1016/j.chembiol.2015.08.018
文献子类	Article
英文摘要	RIP3-dependent necroptosis has recently garnered significant interest because of the unique signaling mechanisms and pathologic functions involved in this process. Accordingly, a number of chemical screens have identified several effective small-molecule inhibitors that specifically block necroptosis. Here, we report the discovery that kongensin A (KA), a natural product isolated from Croton kongensis, is a potent inhibitor of necroptosis and an inducer of apoptosis. Using a new bioorthogonal ligation method (TQ ligation), we reveal that the direct cellular target of KA is heat shock protein 90 (HSP90). Further studies demonstrate that KA covalently binds to a previously uncharacterized cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its cochaperone CDC37, which leads to inhibition of RIP3-dependent necroptosis and promotion of apoptosis in multiple cancer cell lines. Collectively, our findings demonstrate that KA is an effective HSP90 inhibitor that has potential anti-necroptosis and anti-inflammation applications.
WOS关键词	MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; CELL-DEATH ; PROGRAMMED NECROSIS ; BIOORTHOGONAL LIGATION ; MOLECULAR CHAPERONE ; RIP3 ; CANCER ; MLKL ; COMPLEX
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000381508000012
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/170342]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Lei, Xiaoguang; Shen, Zhirong
作者单位	1.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China 2.Beijing Normal Univ, Grad Program, Beijing 100875, Peoples R China 3.Natl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China 4.Peking Univ, Beijing Natl Lab Mol Sci, Key Lab Bioorgan Chem & Mol Engn, Minist Educ,Dept Chem Biol,Coll Chem & Mol Engn,S, Beijing 100871, Peoples R China 5.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	Wang, Lei,Li, Dianrong,Li, Chao,et al. Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis[J]. Cell Chemical Biology,2016,23(2):257-266.
APA	Wang, Lei.,Li, Dianrong.,Li, Chao.,Li, Lin.,Chen, She.,...&Shen, Zhirong.(2016).Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis.Cell Chemical Biology,23(2),257-266.
MLA	Wang, Lei,et al."Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis".Cell Chemical Biology 23.2(2016):257-266.