Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0042109 (
urticaria
)
6,569
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action. 2786 53
