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PMID:10334992

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Citation

Makishima, M, Okamoto, AY, Repa, JJ, Tu, H, Learned, RM, Luk, A, Hull, MV, Lustig, KD, Mangelsdorf, DJ and Shan, B (1999) Identification of a nuclear receptor for bile acids. Science 284:1362-5

Abstract

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.

Links

PubMed

Keywords

Animals; Bile Acids and Salts/biosynthesis; Bile Acids and Salts/metabolism; Biological Transport; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Chenodeoxycholic Acid/metabolism; Cholesterol/metabolism; Cholesterol 7-alpha-Hydroxylase/genetics; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Histone Acetyltransferases; Homeostasis; Humans; Hydroxysteroid Dehydrogenases; Ligands; Liver/metabolism; Membrane Glycoproteins; Mice; Nuclear Receptor Coactivator 1; Organic Anion Transporters, Sodium-Dependent; Receptors, Cytoplasmic and Nuclear/chemistry; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Symporters; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Transfection; Tumor Cells, Cultured

Significance

Annotations

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

RAT:NR1H4

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NR1H4

enables

GO:0004879: nuclear receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:NR1H4

enables

GO:0038181: bile acid receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:NR1H4

enables

GO:1902122: chenodeoxycholic acid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:NR1H4

part_of

GO:0043235: receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NR1H4

involved_in

GO:1903413: cellular response to bile acid

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NR1H4

involved_in

GO:0038185: intracellular bile acid receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR1H4

involved_in

GO:0006357: regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0038181: bile acid receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(CHEBI:16755)
  • happens_during:(GO:1903413)

Seeded From UniProt

complete

HUMAN:NR1H4

part_of

GO:0043235: receptor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NR1H4

involved_in

GO:1903413: cellular response to bile acid

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0003714: transcription corepressor activity

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

F

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0003713: transcription coactivator activity

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

F

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0003700: DNA-binding transcription factor activity

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


F

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:1902122: chenodeoxycholic acid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NR1H4

involved_in

GO:0070858: negative regulation of bile acid biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR1H4

involved_in

GO:0038185: intracellular bile acid receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0038181: bile acid receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

activated_by:(CHEBI:28834)

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0038181: bile acid receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

activated_by:(CHEBI:16325)

Seeded From UniProt

complete

HUMAN:NR1H4

enables

GO:0038181: bile acid receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

activated_by:(CHEBI:16755)

Seeded From UniProt

complete


See also

References

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