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PMID:10334993

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Citation

Parks, DJ, Blanchard, SG, Bledsoe, RK, Chandra, G, Consler, TG, Kliewer, SA, Stimmel, JB, Willson, TM, Zavacki, AM, Moore, DD and Lehmann, JM (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science 284:1365-8

Abstract

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.

Links

PubMed

Keywords

Animals; Bile Acids and Salts/chemistry; Bile Acids and Salts/metabolism; Bile Acids and Salts/pharmacology; Carrier Proteins/metabolism; Cell Line; Chenodeoxycholic Acid/metabolism; Chenodeoxycholic Acid/pharmacology; Cholesterol/metabolism; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Deoxycholic Acid/metabolism; Deoxycholic Acid/pharmacology; Histone Acetyltransferases; Homeostasis; Humans; Ligands; Lithocholic Acid/metabolism; Lithocholic Acid/pharmacology; Mice; Nuclear Receptor Coactivator 1; Organic Anion Transporters, Sodium-Dependent; Protein Conformation; Receptors, Cytoplasmic and Nuclear/chemistry; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Recombinant Fusion Proteins/metabolism; Signal Transduction; Structure-Activity Relationship; Symporters; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NR1H4

enables

GO:0004879: nuclear receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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