Home LiteratureArticle Details
PMID: 12799447 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Alternatively spliced isoforms of the human constitutive androstane receptor.

Nucleic acids research ·Vol. 31 ·No. 12 ·2003-06-15 ·Pages 3194-207

Auerbach SS, Ramsden R, Stoner MA, Verlinde C, Hassett C, Omiecinski CJ

Abstract

The nuclear receptor CAR (NR1I3) regulates transcription of genes encoding xenobiotic- and steroid-metabolizing enzymes. Regulatory processes that are mediated by CAR are modulated by a structurally diverse array of chemicals including common pharmaceutical and environmental agents. Here we describe four in-frame splice variants of the human CAR receptor gene. The variant mRNA splice transcripts were expressed in all human livers evaluated. Molecular modeling of the splice variant proteins predicts that the structural effects are localized within the receptor's ligand-binding domain. Assays to assess function indicate that the variant proteins, when compared with the reference protein isoform, exhibit compromised activities with respect to DNA binding, transcriptional activation and coactivator recruitment.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence Blotting, Western COS Cells Cloning, Molecular Constitutive Androstane Receptor DNA/metabolism Histone Acetyltransferases Humans Ligands Liver/chemistry Models, Molecular Molecular Sequence Data Nuclear Receptor Coactivator 1 Protein Isoforms/genetics,metabolism Protein Structure, Tertiary RNA, Messenger/analysis,chemistry,metabolism Receptors, Cytoplasmic and Nuclear/chemistry,genetics,metabolism Recombinant Proteins/metabolism Sequence Alignment Transcription Factors/chemistry,genetics,metabolism Transcriptional Activation
Chemicals
Constitutive Androstane Receptor Ligands NR1I3 protein, human Protein Isoforms RNA, Messenger Receptors, Cytoplasmic and Nuclear Recombinant Proteins Transcription Factors DNA Histone Acetyltransferases NCOA1 protein, human Nuclear Receptor Coactivator 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Auerbach Scott S
Department of Pharmacology, University of Washington, Seattle, WA, USA.
Ramsden Richard
Stoner Matthew A
Verlinde Christophe
Hassett Christopher
Omiecinski Curtis J
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkg419
Published
2003-06-15
Pages
3194-207
Language
English
Region
England
NLM ID
0411011
PMCID
PMC162252
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066411 · United States
NIEHS NIH HHS · ES07033 · United States
NIEHS NIH HHS · ES07032 · United States
NIEHS NIH HHS · T32 ES007032 · United States
NIGMS NIH HHS · GM66411 · United States
NIEHS NIH HHS · P30 ES007033 · United States
External Links
PubMed source DOI: 10.1093/nar/gkg419 PMC Full Text View journal details
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