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Transcriptional regulation of the intestinal nuclear bile acid farnesoid X receptor (FXR) by the caudal-related homeobox 2 (CDX2).
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2014 Oct 10; Vol. 289 (41), pp. 28421-32. Date of Electronic Publication: 2014 Aug 19. - Publication Year :
- 2014
-
Abstract
- Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor superfamily. It is highly expressed in the enterohepatic system, where it senses bile acid levels to consequently reduce their synthesis while inducing their detoxification. Bile acids are intestinal tumor promoters and their concentrations have to be tightly regulated. Indeed, reduced expression of FXR in the intestine increases colorectal cancer susceptibility in mice, whereas its activation can promote apoptosis in genetically modified cells. Notably, despite the broad knowledge of the FXR enterohepatic transcriptional activity, the molecular mechanisms regulating FXR expression in the intestine are still unknown. Herein, by combining both gain and loss of function approaches and FXR promoter activity studies, we identified caudal-related homeobox 2 (CDX2) transcription factor as a positive regulator of FXR expression in the enterocytes. Our results provide a putative novel tool for modulating FXR expression against bile acid-related colorectal cancer progression.<br /> (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Adenomatous Polyposis Coli metabolism
Adenomatous Polyposis Coli pathology
Adenomatous Polyposis Coli Protein genetics
Adenomatous Polyposis Coli Protein metabolism
Animals
Bile Acids and Salts metabolism
Binding Sites
CDX2 Transcription Factor
Cell Line, Tumor
Homeodomain Proteins metabolism
Humans
Intestinal Mucosa metabolism
Intestines pathology
Mice
Mice, Transgenic
Promoter Regions, Genetic
Protein Binding
Receptors, Cytoplasmic and Nuclear metabolism
Signal Transduction
Transcription Factors metabolism
Adenomatous Polyposis Coli genetics
Gene Expression Regulation, Neoplastic
Homeodomain Proteins genetics
Receptors, Cytoplasmic and Nuclear genetics
Transcription Factors genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 289
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25138215
- Full Text :
- https://doi.org/10.1074/jbc.M114.571513