PPAR-alpha Gene Regulation Pathway

Preferred Label : PPAR-alpha Gene Regulation Pathway;

NCIt synonyms : PPARA Gene Regulation Pathway; PPARa-alpha Gene Regulation Pathway;

NCIt related terms : Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha);

Alternative definition : BIOCARTA: The most recognized mechanism by which peroxisome proliferators regulate gene expression is through a PPAR/RXR heterodimeric complex binding to a peroxisome proliferator-response element (PPRE) (classical mechanism). However, there is the possibility of several variations on this theme: 1) the peroxisome proliferator interacts with PPAR that preexists as a DNA complex with associated corepressors proteins. The interaction with ligand causes release of the corepressor and association with a coactivator, resulting in the classical mechanism. 2) the peroxisome proliferator interacts with PPAR as a soluble member of the nucleus. The binding of ligand results in RXR heterodimerization, DNA binding and coactivator recruitment. 3) in this scenario, PPAR exists in the cytosol, perhaps complexed to heat shock protein 90 and/or other chaperones. Binding of peroxisome proliferator causes a conformational change and translocation into the nucleus. Scenarios 4 and 5 require regulation of gene expression via non-classical mechanisms: 4) PPAR is capable of interacting with, and forming DNA binding heterodimers with, several nuclear receptors including the thyroid hormone receptor. The binding site for this non-RXR heterodimer need not be the classic DR-1 motif found in the PPRE. 5) PPAR may participate in the regulation of gene expression without binding to DNA. By association with transcription factors such as c-jun or p65, PPAR diminishes the ability of AP1 or NFB to bind to their cognate DNA sequences, respectively. Also shown in this scheme are two means to modify the peroxisome proliferator response. Most importantly, growth factor signaling has a pronounced affect on PPAR via post-translational modification. PPAR is a phosphoprotein and its activity is affected by insulin. Several kinase pathways affect PPARa's activity, although the specific kinases and phosphorylation sites have not been conclusively determined. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_pparaPathway;

Details

Origin ID

C39197;

UMLS CUI

C1518805;

Semantic type(s)
- Genetic Function [UMLS semantic type]
has_gene_product_element
- CREB-Binding Protein [NCIt concept]
- Cbp/p300-Interacting Transactivator 2 [NCIt concept]
- Dual Specificity Protein Phosphatase 1 [NCIt concept]
- Fatty Acid-Binding Protein, Liver [NCIt concept]
- Heat Shock 70 kDa Protein 1A/1B [NCIt concept]
- Histone Acetyltransferase p300 [NCIt concept]
- Insulin [NCIt concept]
- Lipopolysaccharide-Binding Protein [NCIt concept]
- Lipoprotein Lipase [NCIt concept]
- Mediator of RNA Polymerase II Transcription Subunit 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Myc Proto-Oncogene Protein [NCIt concept]
- NADP-Dependent Malic Enzyme [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Nitric Oxide Synthase, Inducible [NCIt concept]
- Nuclear Receptor Coactivator 1 [NCIt concept]
- Nuclear Receptor Corepressor 1 [NCIt concept]
- Nuclear Receptor Corepressor 2 [NCIt concept]
- Nuclear Receptor-Interacting Protein 1 [NCIt concept]
- Oxysterols Receptor LXR-Alpha [NCIt concept]
- Peroxisome Proliferator-Activated Receptor Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- Platelet-Derived Growth Factor Subunit A [NCIt concept]
- Prostaglandin G/H Synthase 2 [NCIt concept]
- Protease-Activated Receptor 1 [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- Retinoblastoma-Associated Protein [NCIt concept]
- Retinoic Acid Receptor RXR-Alpha [NCIt concept]
- Signal Transducer and Activator of Transcription 5B [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Transcription Factor Sp1 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
- cAMP-Dependent Protein Kinase Type II-Alpha Regulatory Subunit [NCIt concept]
pathway_has_gene_element
- CITED2 wt Allele [NCIt concept]
- CREBBP wt Allele [NCIt concept]
- DUSP1 wt Allele [NCIt concept]
- EP300 wt Allele [NCIt concept]
- F2R wt Allele [NCIt concept]
- FABP1 wt Allele [NCIt concept]
- HSPA1A wt Allele [NCIt concept]
- HSPA1B wt Allele [NCIt concept]
- INS wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- LBP wt Allele [NCIt concept]
- LPL wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- ME1 wt Allele [NCIt concept]
- MED1 wt Allele [NCIt concept]
- MYC wt Allele [NCIt concept]
- NCOA1 wt Allele [NCIt concept]
- NCOR1 wt Allele [NCIt concept]
- NCOR2 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- NOS2 wt Allele [NCIt concept]
- NR0B2 wt Allele [NCIt concept]
- NR1H3 wt Allele [NCIt concept]
- NRIP1 wt Allele [NCIt concept]
- PDGFA wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PPARA wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]
- PTGS2 wt Allele [NCIt concept]
- RB1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- RXRA wt Allele [NCIt concept]
- SP1 wt Allele [NCIt concept]
- STAT5B wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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