Editing Peroxisome proliferator-activated receptor (section)

== Physiological function ==
All PPARs [[heterodimerize]] with the [[retinoid X receptor]] (RXR) and bind to specific regions on the [[DNA]] of target genes.  These DNA sequences are termed PPREs (peroxisome proliferator [[hormone response element]]s). The DNA [[consensus sequence]] is AGGTCANAGGTCA, with N being any [[nucleotide]]. In general, this sequence occurs in the promoter region of a [[gene]], and, when the ''PPAR'' binds its ligand, [[transcription (genetics)|transcription]] of target genes is increased or decreased, depending on the gene. The RXR also forms a [[heterodimer]] with a number of other receptors (e.g., [[calcitriol receptor|vitamin D]] and [[thyroid hormone receptor|thyroid hormone]]).

The function of PPARs is modified by the precise shape of their ligand-binding domain (see below) induced by ligand binding and by a number of [[coactivator (genetics)|coactivator]] and [[corepressor (genetics)|corepressor]] proteins, the presence of which can stimulate or inhibit receptor function, respectively.<ref name="pmid17306620">{{cite journal | vauthors = Yu S, Reddy JK | title = Transcription coactivators for peroxisome proliferator-activated receptors | journal = Biochim. Biophys. Acta | volume = 1771 | issue = 8 | pages = 936–51 | year = 2007 | pmid = 17306620 | doi = 10.1016/j.bbalip.2007.01.008 }}</ref>

Endogenous ligands for the PPARs include [[free fatty acid]]s, [[eicosanoid]]s and [[Vitamin B3]]. [[PPARγ]] is activated by PGJ<sub>2</sub> (a [[prostaglandin]]) and certain members of the [[5-HETE]] family of [[arachidonic acid]] metabolites including 5-oxo-15(S)-HETE and 5-oxo-ETE.<ref>Biochim. Biophys. Acta 1736:228–236, 2005</ref> In contrast, PPARα is activated by [[leukotriene]] B<sub>4</sub>.  Certain members of the [[15-Hydroxyeicosatetraenoic acid|15-hydroxyeicosatetraenoic acid]] family of arachidonic acid metabolites, including 15(S)-HETE, 15(R)-HETE, and 15-HpETE activate to varying degrees PPAR alpha, beta/delta, and gamma. In addition, [[PPARγ]] was reported to be involved in cancer pathogenesis and growth.<ref >{{cite journal | vauthors = Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee, MJ | title = Downregulation of fatty acid oxidation by involvement of HIF-1α and PPARγ in human gastric adenocarcinoma and its related clinical significance | journal = Journal of Physiology and Biochemistry | volume = 77 | issue = 2 | pages = 249–260 | date = May 2021 | pmid =  33730333 | doi = 10.1007/s13105-021-00791-3 | s2cid = 232300877 | url = https://pubmed.ncbi.nlm.nih.gov/33730333/| issn = }}</ref><ref>Mol. Pharmacol. 77-171-184, 2010</ref> [[PPARγ]] activation by agonist RS5444 may inhibit anaplastic thyroid cancer growth.<ref name="pmid19208833">{{cite journal | vauthors = Marlow LA, Reynolds LA, Cleland AS, Cooper SJ, Gumz ML, Kurakata S, Fujiwara K, Zhang Y, Sebo T, Grant C, McIver B, Wadsworth JT, Radisky DC, Smallridge RC, Copland JA | title = Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth | journal = Cancer Res. | volume = 69 | issue = 4 | pages = 1536–44 |date=February 2009 | pmid = 19208833 | doi = 10.1158/0008-5472.CAN-08-3718 | pmc = 2644344 }}</ref> See<ref>Curr. Mol. Med. 7:532–540, 2007</ref> for a review and critique of the roles of PPAR gamma in cancer.