Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR

Matthew D Krasowski; Ai Ni; Lee R Hagey; Sean Ekins

doi:10.1016/j.mce.2010.06.016

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Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR

Journal article

Peer reviewed

Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR

Matthew D Krasowski, Ai Ni, Lee R Hagey and Sean Ekins

Molecular and cellular endocrinology, Vol.334(1), pp.39-48

2011

DOI: 10.1016/j.mce.2010.06.016

PMCID: PMC3033471

PMID: 20615451

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Abstract

Nuclear hormone receptors (NHRs) are transcription factors that work in concert with co-activators and co-repressors to regulate gene expression. Some examples of ligands for NHRs include endogenous compounds such as bile acids, retinoids, steroid hormones, thyroid hormone, and vitamin D. This review describes the evolution of liver X receptors α and β (NR1H3 and 1H2, respectively), farnesoid X receptor (NR1H4), vitamin D receptor (NR1I1), pregnane X receptor (NR1I2), and constitutive androstane receptor (NR1I3). These NHRs participate in complex, overlapping transcriptional regulation networks involving cholesterol homeostasis and energy metabolism. Some of these receptors, particularly PXR and CAR, are promiscuous with respect to the structurally wide range of ligands that act as agonists. A combination of functional and computational analyses has shed light on the evolutionary changes of NR1H and NR1I receptors across vertebrates, and how these receptors may have diverged from ancestral receptors that first appeared in invertebrates.

Molecular evolution

Ciona intestinalis

Oxysterols

Drug modeling

Phylogeny

Bile acids and salts

Cholesterol

Details

Title: Subtitle: Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR
Creators: Matthew D Krasowski - Department of Pathology, University of Iowa Hospitals and Clinics, RCP 6233, 200 Hawkins Drive, Iowa City, IA 52242, USA
Ai Ni - Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, Piscataway, NJ 08854, USA
Lee R Hagey - Department of Medicine, University of California at San Diego, CA 92093, USA
Sean Ekins - Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, Piscataway, NJ 08854, USA
Resource Type: Journal article
Publication Details: Molecular and cellular endocrinology, Vol.334(1), pp.39-48
DOI: 10.1016/j.mce.2010.06.016
PMID: 20615451
PMCID: PMC3033471
NLM abbreviation: Mol Cell Endocrinol
ISSN: 0303-7207
eISSN: 1872-8057
Publisher: Elsevier Ireland Ltd
Language: English
Date published: 2011
Academic Unit: Pathology
Record Identifier: 9984047622502771

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