A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.
Mol Cell
; 6(3): 517-26, 2000 Sep.
Article
in En
| MEDLINE
| ID: mdl-11030332
ABSTRACT
Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. Although bile acids activate the farnesoid X receptor (FXR), the mechanism underlying bile acid-mediated repression of CYP7A1 remained unclear. We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor that is known to regulate CYP7A1 expression positively. This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Bile Acids and Salts
/
Protein Tyrosine Phosphatases
/
Receptors, Cytoplasmic and Nuclear
/
DNA-Binding Proteins
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2000
Document type:
Article
Affiliation country:
United States