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Indexed by:期刊论文

Date of Publication:2017-05-01

Journal:CHEMICAL BIOLOGY & DRUG DESIGN

Included Journals:SCIE、PubMed、Scopus

Volume:89

Issue:5

Page Number:655-662

ISSN No.:1747-0277

Key Words:caffeic acid phenethyl ester; covalent binding; nuclear export; XPO1; CRM1

Abstract: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.