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Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action
Wu, Sijin1; Zhang, Keren1; Qin, Hongqiang2; Niu, Mingshan1; Zhao, Weijie3; Ye, Mingliang2; Zou, Hanfa2; Yang, Yongliang1
KeywordCaffeic Acid Phenethyl Ester Covalent Binding Nuclear Export Xpo1 Crm1
Source PublicationCHEMICAL BIOLOGY & DRUG DESIGN
2017-05-01
DOI10.1111/cbdd.12905
Volume89Issue:5Pages:655-662
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Medicinal
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS KeywordNUCLEAR EXPORT INHIBITORS ; FACTOR-KAPPA-B ; LEPTOMYCIN-B ; NUCLEOCYTOPLASMIC TRANSPORT ; TRANSCRIPTION FACTOR ; DRUG-RESISTANCE ; CELLS ; CANCER ; DERIVATIVES ; SUPPRESSES
AbstractCaffeic 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.
Language英语
WOS IDWOS:000399734600001
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/152017
Collection中国科学院大连化学物理研究所
Affiliation1.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
Recommended Citation
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.
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