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2016 ; 1859
(9
): 1130-1140
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Mechanisms of xenobiotic receptor activation: Direct vs indirect
#MMPMID26877237
Mackowiak B
; Wang H
Biochim Biophys Acta
2016[Sep]; 1859
(9
): 1130-1140
PMID26877237
show ga
The so-called xenobiotic receptors (XRs) have functionally evolved into cellular
sensors for both endogenous and exogenous stimuli by regulating the transcription
of genes encoding drug-metabolizing enzymes and transporters, as well as those
involving energy homeostasis, cell proliferation, and/or immune responses. Unlike
prototypical steroid hormone receptors, XRs are activated through both direct
ligand-binding and ligand-independent (indirect) mechanisms by a plethora of
structurally unrelated chemicals. This review covers research literature that
discusses direct vs. indirect activation of XRs. A particular focus is centered
on the signaling control of the constitutive androstane receptor (CAR), the
pregnane X receptor (PXR), and the aryl hydrocarbon receptor (AhR). We expect
that this review will shed light on both the common and distinct mechanisms
associated with activation of these three XRs. This article is part of a Special
Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited
by Dr. Wen Xie.
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