Fatty acid ligands activate PPARA

Stable Identifier
R-HSA-400143
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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PPAR-alpha is activated by binding polyunsaturated fatty acids especially those having 18-22 carbon groups and 2-6 double bonds. These ligands bind the C-terminal region of PPAR-alpha and include linoleic acid, linolenic acids, arachidonic acid, and eicosapentaenoic acid. The fibrate drugs are also agonists of PPAR-alpha.
Binding of a ligand causes a conformational change in PPAR-alpha so that it recruits coactivators. By analogy with the closely related receptor PPAR-gamma, PPAR-alpha probably binds TBL1 and TBLR1, which are responsible for recruiting the 19S proteasome to degrade corepressors during the exchange of corepressors for coactivators. The coactivators belong to the CBP-SRC-HAT complex (CBP/p300, SRC1, SRC2, SRC3, CARM1, SWI/SNF, BAF60C, PRIC320, and PRIC285), the ASC complex (PRIP/ASC2, PIMT), and the TRAP-DRIP-ARC-MEDIATOR complex (TRAP130, PBP/TRAP220). The coactivators contain LXXLL motifs (Nuclear Receptor Boxes) that interact with the AF-2 region in nuclear receptors such as PPAR-alpha.

Literature References
PubMed ID Title Journal Year
17306620 Transcription coactivators for peroxisome proliferator-activated receptors

Yu, S, Reddy, JK

Biochim Biophys Acta 2007
19289416 L-FABP directly interacts with PPARalpha in cultured primary hepatocytes

Hostetler, HA, McIntosh, AL, Atshaves, BP, Storey, SM, Payne, HR, Kier, AB, Schroeder, F

J Lipid Res 2009
18288277 Peroxisome proliferator activated receptors and lipoprotein metabolism

Kersten, S

PPAR Res 2008
11330046 Peroxisome proliferator-activated receptors, coactivators, and downstream targets

Qi, C, Zhu, Y, Reddy, JK

Cell Biochem Biophys 2000
14980219 A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors

Perissi, V, Aggarwal, A, Glass, CK, Rose, DW, Rosenfeld, MG

Cell 2004
11226238 Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha - and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus

Wolfrum, C, Borrmann, CM, Borchers, T, Spener, F

Proc Natl Acad Sci U S A 2001
10529898 Peroxisome proliferator-activated receptors: nuclear control of metabolism

Desvergne, B, Wahli, W

Endocr Rev 1999
9171241 Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay

Krey, G, Braissant, O, L'Horset, F, Kalkhoven, E, Perroud, M, Parker, MG, Wahli, W

Mol Endocrinol 1997
17007889 Selectivity of fatty acid ligands for PPARalpha which correlates both with binding to cis-element and DNA binding-independent transactivity in Caco-2 cells

Mochizuki, K, Suruga, K, Fukami, H, Kiso, Y, Takase, S, Goda, T

Life Sci 2006
16476485 From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions

Feige, JN, Gelman, L, Michalik, L, Desvergne, B, Wahli, W

Prog Lipid Res 2006
16503871 Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis

Gouni-Berthold, I, Krone, W

Curr Drug Targets Cardiovasc Haematol Disord 2005
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