country

Change Language

EN - English
FR - Français
DE - Deutsch
ES - Español
JA - 日本語
KO - 한국어

Country or Region:

United States

Product Name	Size / Unit Price	Qty

Total: USD 0.00 Checkout

Bile acid receptor

Definition:

Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (By similarity). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (By similarity). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression (By similarity). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3) (By similarity). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (By similarity). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling) (By similarity).; [Isoform 1]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.; [Isoform 2]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA.; [Isoform 3]: Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA.; [Isoform 4]: Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.

References:

[1]. M Makishima, et al. Identification of a nuclear receptor for bile acids. Science. 1999 May 21;284(5418):1362-5. [Content Brief]

[2]. D J Parks, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999 May 21;284(5418):1365-8. [Content Brief]

[3]. Salvatore Modica, et al. Deciphering the nuclear bile acid receptor FXR paradigm. Nucl Recept Signal. 2010 Nov 19;8:e005. [Content Brief]

[4]. Parinaz C Pircher, et al. Farnesoid X receptor regulates bile acid-amino acid conjugation. J Biol Chem. 2003 Jul 25;278(30):27703-11. [Content Brief]

[5]. Piero Vavassori, et al. The bile acid receptor FXR is a modulator of intestinal innate immunity. J Immunol. 2009 Nov 15;183(10):6251-61. [Content Brief]

[6]. Indumathi Chennamsetty, et al. Farnesoid X receptor represses hepatic human APOA gene expression. J Clin Invest. 2011 Sep;121(9):3724-34. [Content Brief]

[7]. Michael Downes, et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003 Apr;11(4):1079-92. [Content Brief]

[8]. Thierry Claudel, et al. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology. 2003 Aug;125(2):544-55. [Content Brief]

[9]. Ezequiel Neimark, et al. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology. 2004 Jul;40(1):149-56. [Content Brief]

[10]. Jonathan Y Bass, et al. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2969-73. [Content Brief]

[11]. Adwoa Akwabi-Ameyaw, et al. FXR agonist activity of conformationally constrained analogs of GW 4064. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4733-9. [Content Brief]

[12]. Jane-L Lew, et al. The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. J Biol Chem. 2004 Mar 5;279(10):8856-61. [Content Brief]

[13]. Andrew M Anisfeld, et al. Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor. J Biol Chem. 2003 May 30;278(22):20420-8. [Content Brief]

[14]. Danielle A A Hollman, et al. Anti-inflammatory and metabolic actions of FXR: insights into molecular mechanisms. Biochim Biophys Acta. 2012 Nov;1821(11):1443-52. [Content Brief]

[15]. Natalia Gomez-Ospina, et al. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun. 2016 Feb 18;7:10713. [Content Brief]

[16]. Jason A Holt, et al. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 2003 Jul 1;17(13):1581-91. [Content Brief]

[17]. Iuliana Ristea Popescu, et al. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS Lett. 2010 Jul 2;584(13):2845-51. [Content Brief]

[18]. Raffaella M Gadaleta, et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut. 2011 Apr;60(4):463-72. [Content Brief]

[19]. Olivier Barbier, et al. FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Gastroenterology. 2003 Jun;124(7):1926-40. [Content Brief]

[20]. Adwoa Akwabi-Ameyaw, et al. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43. [Content Brief]

[21]. Thierry Claudel, et al. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest. 2002 Apr;109(7):961-71. [Content Brief]

[22]. Meenakshisundaram Ananthanarayanan, et al. Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1. J Biol Chem. 2004 Dec 24;279(52):54348-57. [Content Brief]

[23]. Masaaki Miyata, et al. Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase. Drug Metab Pharmacokinet. 2006 Aug;21(4):315-23. [Content Brief]

[24]. Sabyasachi Sanyal, et al. Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15665-70. [Content Brief]

[25]. Kwang-Hoon Song, et al. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology. 2009 Jan;49(1):297-305. [Content Brief]

[26]. H R Kast, et al. Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids. Mol Endocrinol. 2001 Oct;15(10):1720-8. [Content Brief]

[27]. Javier Vaquero, et al. Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition. Biochem Pharmacol. 2013 Oct 1;86(7):926-39. [Content Brief]

[28]. Inés Pineda Torra, et al. Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor. Mol Endocrinol. 2003 Feb;17(2):259-72. [Content Brief]

[29]. Jean-François Landrier, et al. The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes. Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G476-85. [Content Brief]

[30]. J Grober, et al. Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer. J Biol Chem. 1999 Oct 15;274(42):29749-54. [Content Brief]

[31]. Hisako Hirokane, et al. Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J Biol Chem. 2004 Oct 29;279(44):45685-92. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #