Wedelolactone, a Naturally Occurring Coumestan, Enhances Interferon-gamma Signaling through Inhibiting STAT1 Protein Dephosphorylation

doi:10.1074/jbc.M112.442970

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Wedelolactone, a Naturally Occurring Coumestan, Enhances Interferon-gamma Signaling through Inhibiting STAT1 Protein Dephosphorylation
	Chen, Zhimin 1; Sun, Xiaoxiao 1; Shen, Shensi 1; Zhang, Haohao 1; Ma, Xiuquan 2; Liu, Jingli 1; Kuang, Shan 1; Yu, Qiang1
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2013-05-17
卷号	288 期号:20 页码:14417-14427
ISSN号	0021-9258
DOI	10.1074/jbc.M112.442970
文献子类	Article
英文摘要	Signal transducers and activators of transcription 1 (STAT1) transduces signals from cytokines and growth factors, particularly IFN-gamma, and regulates expression of genes involved in cell survival/death, proliferation, and migration. STAT1 is activated through phosphorylation on its tyrosine 701 by JAKs and is inactivated through dephosphorylation by tyrosine phosphatases. We discovered a natural compound, wedelolactone, that increased IFN-gamma signaling by inhibiting STAT1 dephosphorylation and prolonging STAT1 activation through specific inhibition of T-cell protein tyrosine phosphatase (TCPTP), an important tyrosine phosphatase for STAT1 dephosphorylation. More interestingly, wedelolactone inhibited TCPTP through interaction with the C-terminal autoinhibition domain of TCPTP. We also found that wedelolactone synergized with IFN-gamma to induce apoptosis of tumor cells. Our data suggest a new target for anticancer or antiproliferation drugs, a new mechanism to regulate PTPs specifically, and a new drug candidate for treating cancer or other proliferation disorders.
资助项目	China Ministry of Science and Technology Key New Drug Creation and Manufacturing Program Grant[2013ZX09102015] ; China Ministry of Science and Technology Research Grant[2013ZX10002010-009] ; China National Natural Science Foundation[31129004] ; China National Natural Science Foundation[91129701] ; China National Natural Science Foundation[91213304] ; National Science and Technology 973[2012CB910704] ; National Science and Technology 973[2013CB910900]
WOS关键词	TYROSINE-PHOSPHATASE TCPTP ; CELL-GROWTH ; INSULIN SENSITIVITY ; NEGATIVE REGULATION ; PROSTATE-CANCER ; IN-VITRO ; ACTIVATION ; MICE ; APOPTOSIS ; IDENTIFICATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000319253500045
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277616]
专题	药理学第一研究室
通讯作者	Yu, Qiang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Zhimin,Sun, Xiaoxiao,Shen, Shensi,et al. Wedelolactone, a Naturally Occurring Coumestan, Enhances Interferon-gamma Signaling through Inhibiting STAT1 Protein Dephosphorylation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(20):14417-14427.
APA	Chen, Zhimin.,Sun, Xiaoxiao.,Shen, Shensi.,Zhang, Haohao.,Ma, Xiuquan.,...&Yu, Qiang.(2013).Wedelolactone, a Naturally Occurring Coumestan, Enhances Interferon-gamma Signaling through Inhibiting STAT1 Protein Dephosphorylation.JOURNAL OF BIOLOGICAL CHEMISTRY,288(20),14417-14427.
MLA	Chen, Zhimin,et al."Wedelolactone, a Naturally Occurring Coumestan, Enhances Interferon-gamma Signaling through Inhibiting STAT1 Protein Dephosphorylation".JOURNAL OF BIOLOGICAL CHEMISTRY 288.20(2013):14417-14427.