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peroxisome proliferator-activated receptor (PPAR)

Function: - activated by fatty acids & peroxisome proliferators - binds to DNA as heterodimer with RXR - activated PPAR-alpha/RXR: a) may compete other nuclear receptors for RXRE enhancer elements (improper fit may bind without activation) b) induce peroxisome proliferation c) induction of fatty acid metabolism 1] beta-oxidation of fatty acids 2] omega-oxidation of fatty acids - like other nuclear hormone receptors, PPAR are also regulated by coactivators & corepressors, which act as bridging proteins between the receptors & the transcriptional apparatus. - coactivators & corepressors differ for the different PPARs - coactivators include: a) p300/CBP b) tuberous sclerosis-2 protein c) PPAR-binding protein d) PGC-1* e) PGC-2* f) Ara70* g) steroid coactivator-1 (SRC-1) * uncertain as to identity of these proteins

Interactions

molecular events

Related

CREB-binding protein; CBP transcriptional coactivator (CREBBP, CBP) histone acetyltransferase p300; p300 HAT; E1A-associated protein p300 (EP300, P300) mediator of RNA polymerase II transcription subunit 1; activator-recruited cofactor 205 kD component; ARC205; mediator complex subunit 1; peroxisome proliferator-activated receptor-binding protein; PBP; PPAR-binding protein; thyroid hormone receptor-associated protein complex 220 kD component; trap220; thyroid receptor-interacting protein 2; TR-interacting protein 2; TRIP-2; vitamin D receptor-interacting protein complex component DRIP205; p53 regulatory protein RB18A (MED1, ARC205, CRSP1, CRSP200, DRIP205, DRIP230, PBP, PPARBP, PPARGBP, RB18A, TRAP220, TRIP2) nuclear receptor coactivator 1; NCoA-1; steroid receptor coactivator 1; SRC-1; RIP160; protein Hin-2; renal carcinoma antigen NY-REN-52; class E basic helix-loop-helix protein 74; bHLHe74 (NCOA1, BHLHE74, SRC1) peroxisome peroxisome proliferator; PPAR agonist; PPAR gamma agonist retinoid X receptor (RXR) tuberin; tuberous sclerosis 2 protein (TSC2 TSC4)

Specific

peroxisome proliferator-activated receptor alpha; PPAR-alpha; nuclear receptor subfamily 1 group C member 1 (PPARA, NR1C1, PPAR) peroxisome proliferator-activated receptor delta; PPAR-delta; PPAR-beta; nuclear receptor subfamily 1 group C member 2; nuclear hormone receptor 1; NUC1; NUCI (PPARD, NR1C2, PPARB) peroxisome proliferator-activated receptor gamma; PPAR-gamma; nuclear receptor subfamily 1 group C member 3 (PPARG, NR1C3)

General

nuclear hormone receptor NR1 subfamily redox-modulated transcription factor

Properties

COMPARTMENT: cytoplasm MOTIF: allosteric site DNA-binding motif MOTIF: kxffkr NAME: kxffkr FOR-BINDING-OF: calreticulin FORM: kxffkr Zinc finger NAME: Zinc finger (2) EFFECTOR-BOUND: Zn+2 ligand-binding site EFFECTOR-BOUND: fatty acid MISC-INFO: Kd [ETYA] 1 UM Kd [arachidonate] 10 Kd [WY14643] 10

References

  1. Green S. Nuclear hormone receptors. Promiscuous liaisons. Nature. 1993 Feb 18;361(6413):590-1. PMID: 8382343
  2. Nebert DW. Proposed role of drug-metabolizing enzymes: regulation of steady state levels of the ligands that effect growth, homeostasis, differentiation, and neuroendocrine functions. Mol Endocrinol. 1991 Sep;5(9):1203-14. Review. PMID: 1663211
  3. Keller H, Dreyer C, Medin J, Mahfoudi A, Ozato K, Wahli W. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor- retinoid X receptor heterodimers. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2160-4. PMID: 8384714
  4. Corton JC, Anderson SP, Stauber A. Central role of peroxisome proliferator-activated receptors in the actions of peroxisome proliferators. Annu Rev Pharmacol Toxicol. 2000;40:491-518. Review. PMID: 10836145

Component-of

molecular complex