Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action

doi:10.1111/cbdd.12905

	Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action
	Wu, Sijin 1; Zhang, Keren 1; Qin, Hongqiang 2; Niu, Mingshan 1; Zhao, Weijie 3; Ye, Mingliang 2; Zou, Hanfa 2; Yang, Yongliang 1
刊名	CHEMICAL BIOLOGY & DRUG DESIGN
	2017-05-01
卷号	89 期号:5 页码:655-662
关键词	Caffeic Acid Phenethyl Ester Covalent Binding Nuclear Export Xpo1 Crm1
DOI	10.1111/cbdd.12905
英文摘要	Caffeic acid phenethyl ester (CAPE) is the bioactive constituent of propolis from honeybee hives and is well known for its anti-inflammatory, anticarcinogenic, antioxidant, and immunomodulatory properties. Herein, we revisited the cellular mechanism underlying the diverse biological effects of CAPE. We demonstrated that XPO1/CRM1, a major nuclear export receptor, is a cellular target of CAPE. Through nuclear export functional assay, we observed a clear shift of XPO1 cargo proteins from a cytoplasmic localization to nucleus when treated with CAPE. In particular, we showed that CAPE could specifically target the non-catalytic and conserved Cys(528) of XPO1 through the means of mass spectrometric analysis. In addition, we demonstrated that the mutation of Cys(528) residue in XPO1 could rescue the nuclear export defects caused by CAPE. Furthermore, we performed position-restraint molecular dynamics simulation to show that the Michael acceptor moiety of CAPE is the warhead to enable covalent binding with Cys(528) residue of XPO1. The covalent modulation of nuclear export by CAPE may explain its diverse biological effects. Our findings may have general implications for further investigation of CAPE and its structural analogs.
语种	英语
WOS记录号	WOS:000399734600001
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/152017]
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
作者单位	1.Dalian Univ Technol, Sch Life Sci & Biotechnol, Ctr Mol Med, Dalian, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog R&A Ctr, Dalian, Peoples R China 3.Dalian Univ Technol, Sch Pharmacol, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Wu, Sijin,Zhang, Keren,Qin, Hongqiang,et al. Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2017,89(5):655-662.
APA	Wu, Sijin.,Zhang, Keren.,Qin, Hongqiang.,Niu, Mingshan.,Zhao, Weijie.,...&Yang, Yongliang.(2017).Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action.CHEMICAL BIOLOGY & DRUG DESIGN,89(5),655-662.
MLA	Wu, Sijin,et al."Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action".CHEMICAL BIOLOGY & DRUG DESIGN 89.5(2017):655-662.