Peroxisome proliferator-activated receptor delta

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Peroxisome proliferator-activated receptor delta
PDB rendering based on 1gwx.
Available structures: 1gwx, 1y0s, 2awh, 2b50, 2baw, 2gwx, 2j14, 3gwx
Identifiers
Symbol(s) PPARD; FAAR; MGC3931; NR1C2; NUC1; NUCI; NUCII; PPAR-beta; PPARB
External IDs OMIM: 600409 MGI: 101884 HomoloGene: 4544
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 5467 19015
Ensembl ENSG00000112033 ENSMUSG00000002250
Uniprot Q03181 Q546I3
Refseq NM_006238 (mRNA)
NP_006229 (protein)		 XM_990965 (mRNA)
XP_996059 (protein)
Location Chr 6: 35.42 - 35.5 Mb Chr 17: 27.96 - 28.03 Mb
Pubmed search [1] [2]

Peroxisome proliferator-activated receptor delta (PPAR-delta or PPAR-beta), also known as NR1C2 (nuclear receptor subfamily 1, group C, member 2) is a nuclear receptor encoded by the PPARD gene.[1]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. PPARs are nuclear hormone receptors that bind peroxisome proliferators and control the size and number of peroxisomes produced by cells. PPARs mediate a variety of biological processes, and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer.[2][3] This protein is a potent inhibitor of ligand-induced transcription activity of PPAR-α and PPAR-γ. It may function as an integrator of transcription repression and nuclear receptor signaling. The expression of this gene is found to be elevated in colorectal cancer cells.[4] The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein related to APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, epidermal cell proliferation, and glucose[5] and lipid metabolism.[6]


PPAR-delta is the main target of a research chemical named GW501516. It has been shown that agonism of PPAR-delta changes the body's fuel preference from glucose to lipids.[7]

[edit] References

  1. ^ Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA (1992). "Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids". Mol. Endocrinol. 6 (10): 1634–41. doi:10.1210/me.6.10.1634. PMID 1333051. 
  2. ^ Berger J, Moller DE (2002). "The mechanisms of action of PPARs". Annu. Rev. Med. 53: 409–35. doi:10.1146/annurev.med.53.082901.104018. PMID 11818483. 
  3. ^ Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W (2006). "From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions". Prog. Lipid Res. 45 (2): 120–59. doi:10.1016/j.plipres.2005.12.002. PMID 16476485. 
  4. ^ Takayama O, Yamamoto H, Damdinsuren B, Sugita Y, Ngan CY, Xu X, Tsujino T, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M (2006). "Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology". Br. J. Cancer 95 (7): 889–95. doi:10.1038/sj.bjc.6603343. PMID 16969348. 
  5. ^ Lee CH, Olson P, Hevener A, Mehl I, Chong LW, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, Evans RM (2006). "PPARdelta regulates glucose metabolism and insulin sensitivity". Proc. Natl. Acad. Sci. U.S.A. 103 (9): 3444–9. doi:10.1073/pnas.0511253103. PMID 16492734. 
  6. ^ Entrez Gene: PPARD peroxisome proliferator-activated receptor delta.
  7. ^ B. Brunmair et al. (2006). "Activation of PPAR-δ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids". Diabetologia 49 (11): 2713–22. doi:10.1007/s00125-006-0357-6. ISSN (Print) 1432-0428 (Online) 0012-186X (Print) 1432-0428 (Online). 

[edit] Further reading

  • Kersten S, Desvergne B, Wahli W (2000). "Roles of PPARs in health and disease.". Nature 405 (6785): 421–4. doi:10.1038/35013000. PMID 10839530. 
  • Bastie C (2002). "[PPARdelta and PPARgamma: roles in fatty acids signalling, implication in tumorigenesis]". Bulletin du cancer 89 (1): 23–8. PMID 11847022. 
  • Fredenrich A, Grimaldi PA (2004). "Roles of peroxisome proliferator-activated receptor delta in skeletal muscle function and adaptation.". Current opinion in clinical nutrition and metabolic care 7 (4): 377–81. PMID 15192438. 
  • Fredenrich A, Grimaldi PA (2005). "PPAR delta: an uncompletely known nuclear receptor.". Diabetes Metab. 31 (1): 23–7. PMID 15803109. 
  • Barish GD, Narkar VA, Evans RM (2006). "PPAR delta: a dagger in the heart of the metabolic syndrome.". J. Clin. Invest. 116 (3): 590–7. doi:10.1172/JCI27955. PMID 16511591. 
  • Fürnsinn C, Willson TM, Brunmair B (2007). "Peroxisome proliferator-activated receptor-delta, a regulator of oxidative capacity, fuel switching and cholesterol transport.". Diabetologia 50 (1): 8–17. doi:10.1007/s00125-006-0492-0. PMID 17119917. 
  • Takahashi S, Tanaka T, Sakai J (2007). "New therapeutic target for metabolic syndrome: PPARdelta.". Endocr. J. 54 (3): 347–57. PMID 17409576. 
  • Schmidt A, Endo N, Rutledge SJ, et al. (1992). "Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.". Mol. Endocrinol. 6 (10): 1634–41. PMID 1333051. 
  • Jow L, Mukherjee R (1995). "The human peroxisome proliferator-activated receptor (PPAR) subtype NUC1 represses the activation of hPPAR alpha and thyroid hormone receptors.". J. Biol. Chem. 270 (8): 3836–40. PMID 7876127. 
  • Yoshikawa T, Brkanac Z, Dupont BR, et al. (1996). "Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2.". Genomics 35 (3): 637–8. doi:10.1006/geno.1996.0417. PMID 8812511. 
  • Chu R, Lin Y, Rao MS, Reddy JK (1996). "Cloning and identification of rat deoxyuridine triphosphatase as an inhibitor of peroxisome proliferator-activated receptor alpha.". J. Biol. Chem. 271 (44): 27670–6. PMID 8910358. 
  • Tripodis N, Mason R, Humphray SJ, et al. (1999). "Physical map of human 6p21.2-6p21.3: region flanking the centromeric end of the major histocompatibility complex.". Genome Res. 8 (6): 631–43. PMID 9647638. 
  • Xu HE, Lambert MH, Montana VG, et al. (1999). "Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.". Mol. Cell 3 (3): 397–403. PMID 10198642. 
  • He TC, Chan TA, Vogelstein B, Kinzler KW (1999). "PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.". Cell 99 (3): 335–45. PMID 10555149. 
  • Kraus WL, Manning ET, Kadonaga JT (2000). "Biochemical analysis of distinct activation functions in p300 that enhance transcription initiation with chromatin templates.". Mol. Cell. Biol. 19 (12): 8123–35. PMID 10567538. 
  • Skogsberg J, Kannisto K, Roshani L, et al. (2000). "Characterization of the human peroxisome proliferator activated receptor delta gene and its expression.". Int. J. Mol. Med. 6 (1): 73–81. PMID 10851270. 
  • Peters JM, Lee SS, Li W, et al. (2000). "Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).". Mol. Cell. Biol. 20 (14): 5119–28. PMID 10866668. 
  • Yi YW, Kim D, Jung N, et al. (2000). "Gadd45 family proteins are coactivators of nuclear hormone receptors.". Biochem. Biophys. Res. Commun. 272 (1): 193–8. PMID 10872826. 
  • Bastie C, Luquet S, Holst D, et al. (2001). "Alterations of peroxisome proliferator-activated receptor delta activity affect fatty acid-controlled adipose differentiation.". J. Biol. Chem. 275 (49): 38768–73. doi:10.1074/jbc.M006450200. PMID 10991946. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)
ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • Neurogenins • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Scleraxis • TAL1 • Twist • USF1
(1.3) bHLH-ZIP
MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4
GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3)
(2.3) Cys2His2
ATBF1 • BCL(6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF: 1, 2, TFIIH: 1, 2, 4, 2I, 3A, 3C1, 3C2) • GFI1 • GLI-Krüppel family (1, 2, 3, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 4, 5, 6, 9, 10, 11, 12, 13) • MTF1 • MYT1 • OSR1 • Sp1 • zinc finger ((3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 451, 452, 471, 593, 638, 649, 655) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6
(2.5) Alternating composition
AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B
(3) Helix-turn-helix
domains
ARX • CDX (1, 2) • CRX • CUTL1 • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-5, 3-1) • PHF (3, 6, 10, 17) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) • OTX (1, 2) • PDX1
(3.2) Paired box
PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, , O3A, O4, P1, P2, P3)
HSF (1, 2, 4)
(3.5) Tryptophan clusters
ELF (4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(3.6) TEA domain
transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region
NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)
(4.2) STAT
STAT (1, 2, 3, 4, 5, 6)
(4.3) p53
(4.4) MADS box
Mef2 (A, B, C, D) • SRF
HNF (1A, 1B) • LEF1 • SOX (2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 15, 18) • SRY • SSRP1
(4.10) Cold-shock domain
(4.11) Runt
(0) Other
transcription factors
(0.2) HMGI(Y)
HMGA (1, 2) • HBP1
Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-related factors
Apetala 2 • EREBP • B3
(0.6) Miscellaneous
ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFI (A, B, C, X) • NFY (A, B, C) • Rho/Sigma • R-SMAD