Search results for RXRA

Showing 18 results out of 37

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Protein (4 results from a total of 4)

Identifier: R-HSA-381319
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: RXRA: P19793
Identifier: R-HSA-9619757
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: RXRA: P19793
Identifier: R-HSA-5334811
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: RXRA: P19793
Identifier: R-HSA-4341130
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: RXRA: P19793

Reaction (6 results from a total of 19)

Identifier: R-HSA-400204
Species: Homo sapiens
Compartment: nucleoplasm
Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a type II nuclear receptor (its subcellular location is independent of ligand binding) related to PPAR-beta/delta and PPAR-gamma. PPAR-alpha is expressed highly in the liver where if functions to control lipid metabolism, especially fatty acid oxidation.
PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha). The heterodimers bind peroxisome proliferator receptor elements (PPREs) in and around genes regulated by PPAR-alpha.
Identifier: R-HSA-4341048
Species: Homo sapiens
Compartment: nucleoplasm
RXRA (Retinoid X receptor alpha) is SUMOylated at lysine-108 with SUMO1 (Choi et al. 2006). SUMOylation represses transcription activation by RXRA.
Identifier: R-HSA-5340251
Species: Homo sapiens
Compartment: nucleoplasm
The nuclear orphan protein bile acid receptor aka farnesoid X-activated receptor (NR1H4 aka FXR) can be activated by bile acids and their salts, its physiological ligands. Bile acids tested to activate NR1H4 are chenodeoxycholic acid (CDCA), lithocholic acid (LCHA) and deoxycholic acid (DCA) (Parks et al. 1999, Makishima et al. 1999). Once bound to its ligand, activated NR1H4 binds to retinoic acid receptor RXR-alpha (RXRA) and either nuclear receptor coactivator 1 or 2 (NCOA1 or 2) to function as a ligand-activated transcription factor. This complex repressed transcription of the CYP7A1 gene (encoding cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis) (Holt et al. 2003) and activated the SLC10A2 and 6 genes (encoding Ileal sodium/bile acid cotransporters; both bile acid transporters) (Plass et al. 2002, Ananthanarayanan et al. 2001). Thus, NR1H4 is one of the most important regulators of bile acid metabolism, regulating bile acid synthesis, conjugation, secretion and uptake (Lee et al. 2006, Houten et al. 2006).
Identifier: R-HSA-5634100
Species: Homo sapiens
Compartment: nucleoplasm
In the nucleus, all-trans-retinoic acid (atRA), bounds to epidermal fatty acid-binding protein (FABP5), is transferred to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in fatty acid oxidation and energy metabolism via its induction of PPARD (Wolf 2010, Amengual et al. 2012, Noy 2013).
Identifier: R-HSA-5422942
Species: Homo sapiens
Compartment: nucleoplasm
In the nucleus, all-trans-retinoic acid (atRA), bounds to epidermal fatty acid-binding protein (FABP5), is transferred to the heterodimeric complex of retinoic acid receptor alpha RXRA) and peroxisome proliferator-activated receptor delta (PPARD). When bound to PPARD, atRA can significantly increase the expression of proteins involved in fatty acid oxidation and energy metabolism via its induction of PPARD (Wolf 2010, Amengual et al. 2012, Noy 2013).
Identifier: R-HSA-381262
Species: Homo sapiens
Compartment: nucleoplasm
PPARG binds the Retinoic acid X Receptor RXRA to form a heterodimer that has transcriptional acivation activity. The complex was initially called ARF6 when discovered. PPARG binds RXRA via the C-terminus and AF-2 regions of PPARG.

Set (1 results from a total of 1)

Identifier: R-ALL-9844664
Compartment: nucleoplasm

Complex (6 results from a total of 12)

Identifier: R-HSA-9024323
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9024376
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9619754
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9843267
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9843265
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9843268
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (1 results from a total of 1)

Identifier: R-HSA-381340
Species: Homo sapiens
Compartment: nucleoplasm, cytosol, plasma membrane
Adipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develop morphologic and biochemical characteristics of mature adipocytes such as hormone responsive lipogenenic and lipolytic programs. The most intensively studied model system for adipogenesis is differentiation of the mouse 3T3-L1 preadipocyte cell line by an induction cocktail of containing mitogens (insulin/IGF1), glucocorticoid (dexamethasone), an inducer of cAMP (IBMX), and fetal serum (Cao et al. 1991, reviewed in Farmer 2006). More recently additional cellular models have become available to study adipogenesis that involve almost all stages of development (reviewed in Rosen and MacDougald 2006). In vivo knockout mice lacking putative adipogenic factors have also been extensively studied. Human pathways are traditionally inferred from those discovered in mouse but are now beginning to be validated in cellular models derived from human adipose progenitors (Fischer-Posovszky et al. 2008, Wdziekonski et al. 2011).
Adipogenesis is controlled by a cascade of transcription factors (Yeh et al. 1995, reviewed in Farmer 2006, Gesta et al. 2007). One of the first observable events during adipocyte differentiation is a transient increase in expression of the CEBPB (CCAAT/Enhancer Binding Protein Beta, C/EBPB) and CEBPD (C/EBPD) transcription factors (Cao et al. 1991, reviewed in Lane et al. 1999). This occurs prior to the accumulation of lipid droplets. However, it is the subsequent inductions of CEBPA and PPARG that are critical for morphological, biochemical and functional adipocytes.
Ectopic expression of CEBPB alone is capable of inducing substantial adipocyte differentiation in fibroblasts while CEBPD has a minimal effect. CEBPB is upregulated in response to intracellular cAMP (possibly via pCREB) and serum mitogens (possibly via Krox20). CEBPD is upregulated in response to glucocorticoids. The exact mechanisms that upregulate the CEBPs are not fully known.
CEBPB and CEBPD act directly on the Peroxisome Proliferator-activated Receptor Gamma (PPARG) gene by binding its promoter and activating transcription. CEBPB and CEBPD also directly activate the EBF1 gene (and possibly other EBFs) and KLF5 (Jimenez et al. 2007, Oishi 2005). The EBF1 and KLF5 proteins, in turn bind, and activate the PPARG promoter. Other hormones, such as insulin, affect PPARG expression and other transcription factors, such as ADD1/SREBP1c, bind the PPARG promoter. This is an area of ongoing research.
During adipogenesis the PPARG gene is transcribed to yield 2 variants. The adipogenic variant 2 mRNA encodes 30 additional amino acids at the N-terminus compared to the widely expressed variant 1 mRNA.
PPARG encodes a type II nuclear hormone receptor (remains in the nucleus in the absence of ligand) that forms a heterodimer with the Retinoid X Receptor Alpha (RXRA). The heterodimer was initially identified as a complex regulating the aP2/FABP4 gene and named ARF6 (Tontonoz et al. 1994).
The PPARG:RXRA heterodimer binds a recognition sequence that consists of two hexanucleotide motifs (DR1 motifs) separated by 1 nucleotide. Binding occurs even in the absence of ligands, such as fatty acids, that activate PPARG. In the absence of activating ligands, the PPARG:RXRA complex recruits repressors of transcription such as SMRT/NCoR2, NCoR1, and HDAC3 (Tontonoz and Spiegelman 2008).
Each molecule of PPARG can bind 2 molecules of activating ligands. Although, the identity of the endogenous ligands of PPARG is unknown, exogenous activators include fatty acids and the thiazolidinedione class of antidiabetic drugs (reviewed in Berger et al. 2005, Heikkinen et al. 2007, Lemberger et al. 1996). The most potent activators of PPARG in vitro are oxidized derivatives of unsaturated fatty acids.. Upon binding activating ligands PPARG causes a rearrangement of adjacent factors: Corepressors such as SMRT/NCoR2 are lost and coactivators such as TIF2, PRIP, CBP, and p300 are recruited (Tontonoz and Spiegelman). PPARG also binds directly to the TRAP220 subunit of the TRAP/Mediator complex that recruits RNA polymerase II. Thus binding of activating ligand by PPARG causes transcription of PPARG target genes.
Targets of PPARG include genes involved in differentiation (PGAR/HFARP, Perilipin, aP2/FABP4, CEBPA), fatty acid transport (LPL, FAT/CD36), carbohydrate metabolism (PEPCK-C, AQP7, GK, GLUT4 (SLC2A4)), and energy homeostasis (LEPTIN and ADIPONECTIN) (Perera et al. 2006).
Within 10 days of differentiation CEBPB and CEBPD are no longer located at the PPARG promoter. Instead CEBPA is present. EBF1 and PPARG bind the CEBPA promoter and activate transcription of CEBPA, one of the key transcription factors in adipogenesis. A current hypothesis posits a self-reinforcing loop that maintains PPARG expression and the differentiated state: PPARG activates CEBPA and CEBPA activates PPARG. Additionally EBF1 (and possibly other EBFs) activates CEBPA, CEBPA activates EBF1, and EBF1 activates PPARG.
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