liver X receptor alpha

miRNA hsa-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613.http://mend.endojournals.org/content/25/4/584.abstract {{Dead link|date=February 2022}}

The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases.{{cite journal | vauthors = Christoffolete MA, Doleschall M, Egri P, Liposits Z, Zavacki AM, Bianco AC, Gereben B | title = Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway | journal = The Journal of Endocrinology | volume = 205 | issue = 2 | pages = 179–86 | year = 2010 | pmid = 20176747 | pmc = 3133926 | doi = 10.1677/JOE-09-0448 }} The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs) and regulate expression of target genes containing LXR response elements.{{cite journal | vauthors = Korf H, Vander Beken S, Romano M, Steffensen KR, Stijlemans B, Gustafsson JA, Grooten J, Huygen K | title = Liver X receptors contribute to the protective immune response against Mycobacterium tuberculosis in mice | journal = The Journal of Clinical Investigation | volume = 119 | issue = 6 | pages = 1626–37 | date = Jun 2009 | pmid = 19436111 | pmc = 2689129 | doi = 10.1172/JCI35288 }}{{cite web | title = Entrez Gene: nuclear receptor subfamily 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10062}} Restoration of LXR-alpha expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.{{cite journal | vauthors = Gupta DS, Kaul D, Kanwar AJ, Parsad D | title = Psoriasis: crucial role of LXR-alpha RNomics | journal = Genes and Immunity | volume = 11 | issue = 1 | pages = 37–44 | date = Jan 2010 | pmid = 19798078 | doi = 10.1038/gene.2009.63 | doi-access = free }}

Liver X receptor alpha has been shown to interact with EDF1{{cite journal | vauthors = Brendel C, Gelman L, Auwerx J | title = Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism | journal = Molecular Endocrinology | volume = 16 | issue = 6 | pages = 1367–77 | date = Jun 2002 | pmid = 12040021 | doi = 10.1210/mend.16.6.0843 | doi-access = free }} and small heterodimer partner.{{cite journal | vauthors = Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J | title = The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2065–76 | date = Sep 2002 | pmid = 12198243 | doi = 10.1210/me.2001-0194 | doi-access = free }} LXRα activates the transcription factor SREBP-1c, resulting in lipogenesis.{{cite journal | vauthors=Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, Unger RH | title=Leptin therapy in insulin-deficient type I diabetes | journal=Proceedings of the National Academy of Sciences of the United States of America | volume=107 | issue=11 | pages=4813–9 | year=2010 | doi = 10.1073/pnas.0909422107 | pmc=2841945 | pmid=20194735| doi-access=free | bibcode=2010PNAS..107.4813W }}

In 2016, a study found 70% of individuals in two families with a rare form of rapidly progressing multiple sclerosis had a mutation in NR1H3.{{cite journal | vauthors = Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, Yee IM, de Lemos M, Greenwood T, Lee JD, Wright G, Ross CJ, Zhang S, Song W, Vilariño-Güell C | title = Nuclear Receptor NR1H3 in Familial Multiple Sclerosis | journal = Neuron | volume = 90 | issue = 5 | pages = 948–54 | year = 2016 | pmid = 27253448 | pmc = 5092154 | doi = 10.1016/j.neuron.2016.04.039 }} However, an analysis from The International Multiple Sclerosis Genetics Consortium using a 13-fold larger sample size could not find any evidence that the mutation in question (p.Arg415Gln) associated with multiple sclerosis, refuting these findings.{{cite journal | vauthors = Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, Berge T, Bernardinelli L, Booth D, Bos S, Buck D, etal | collaboration = International Multiple Sclerosis Genetics Consortium | title = NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk | journal = Neuron | volume = 92 | issue = 2 | pages = 333–335 | date = October 2016 | pmid = 27764667 | pmc = 5641967 | doi = 10.1016/j.neuron.2016.09.052 }}

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• {{cite journal | vauthors = Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM | title = Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway | journal = The Journal of Biological Chemistry | volume = 272 | issue = 6 | pages = 3137–40 | date = Feb 1997 | pmid = 9013544 | doi = 10.1074/jbc.272.6.3137 | doi-access = free }}
• {{cite journal | vauthors = Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, Staels B, Auwerx J, Laville M, Vidal H | title = Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients | journal = Diabetes | volume = 46 | issue = 8 | pages = 1319–27 | date = Aug 1997 | pmid = 9231657 | doi = 10.2337/diabetes.46.8.1319 }}
• {{cite journal | vauthors = Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ | title = Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha | journal = Cell | volume = 93 | issue = 5 | pages = 693–704 | date = May 1998 | pmid = 9630215 | doi = 10.1016/S0092-8674(00)81432-4 | s2cid = 5856580 | doi-access = free }}
• {{cite journal | vauthors = Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone JP | title = Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha | journal = Molecular and Cellular Endocrinology | volume = 146 | issue = 1–2 | pages = 69–76 | date = Nov 1998 | pmid = 10022764 | doi = 10.1016/S0303-7207(98)00196-8 | s2cid = 53253694 }}
• {{cite journal | vauthors = Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P | title = Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 22 | pages = 12097–102 | date = Oct 2000 | pmid = 11035776 | pmc = 17300 | doi = 10.1073/pnas.200367697 | bibcode = 2000PNAS...9712097V | doi-access = free }}
• {{cite journal | vauthors = Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B | title = PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway | journal = Nature Medicine | volume = 7 | issue = 1 | pages = 53–8 | date = Jan 2001 | pmid = 11135616 | doi = 10.1038/83348 | s2cid = 20558311 }}
• {{cite journal | vauthors = Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P | title = LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 2 | pages = 507–12 | date = Jan 2001 | pmid = 11149950 | pmc = 14617 | doi = 10.1073/pnas.021488798 | doi-access = free }}
• {{cite journal | vauthors = Li Y, Bolten C, Bhat BG, Woodring-Dietz J, Li S, Prayaga SK, Xia C, Lala DS | title = Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism | journal = Molecular Endocrinology | volume = 16 | issue = 3 | pages = 506–14 | date = Mar 2002 | doi = 10.1210/mend.16.3.0789 | pmid = 11875109 | doi-access = free }}
• {{cite journal | vauthors = Mak PA, Laffitte BA, Desrumaux C, Joseph SB, Curtiss LK, Mangelsdorf DJ, Tontonoz P, Edwards PA | title = Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 35 | pages = 31900–8 | date = Aug 2002 | pmid = 12032151 | doi = 10.1074/jbc.M202993200 | doi-access = free }}
• {{cite journal | vauthors = Brendel C, Gelman L, Auwerx J | title = Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism | journal = Molecular Endocrinology | volume = 16 | issue = 6 | pages = 1367–77 | date = Jun 2002 | pmid = 12040021 | doi = 10.1210/mend.16.6.0843 | doi-access = free }}
• {{cite journal | vauthors = Steffensen KR, Schuster GU, Parini P, Holter E, Sadek CM, Cassel T, Eskild W, Gustafsson JA | title = Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins | journal = Biochemical and Biophysical Research Communications | volume = 293 | issue = 5 | pages = 1333–40 | date = May 2002 | pmid = 12054659 | doi = 10.1016/S0006-291X(02)00390-X }}
• {{cite journal | vauthors = Gbaguidi GF, Agellon LB | title = The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1583 | issue = 2 | pages = 229–36 | date = Jul 2002 | pmid = 12117567 | doi = 10.1016/s1388-1981(02)00217-2 }}
• {{cite journal | vauthors = Pawar A, Xu J, Jerks E, Mangelsdorf DJ, Jump DB | title = Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39243–50 | date = Oct 2002 | pmid = 12161442 | doi = 10.1074/jbc.M206170200 | doi-access = free }}
• {{cite journal | vauthors = Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J | title = The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2065–76 | date = Sep 2002 | pmid = 12198243 | doi = 10.1210/me.2001-0194 | doi-access = free }}
• {{cite journal | vauthors = Oberkofler H, Schraml E, Krempler F, Patsch W | title = Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha | journal = The Biochemical Journal | volume = 371 | issue = Pt 1 | pages = 89–96 | date = Apr 2003 | pmid = 12470296 | pmc = 1223253 | doi = 10.1042/BJ20021665 }}
• {{cite journal | vauthors = Wang M, Thomas J, Burris TP, Schkeryantz J, Michael LF | title = Molecular determinants of LXRalpha agonism | journal = Journal of Molecular Graphics & Modelling | volume = 22 | issue = 2 | pages = 173–81 | date = Nov 2003 | pmid = 12932788 | doi = 10.1016/S1093-3263(03)00159-1 | bibcode = 2003JMGM...22..173W }}
• {{cite journal | vauthors = Fukuchi J, Song C, Ko AL, Liao S | title = Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors | journal = Steroids | volume = 68 | issue = 7–8 | pages = 685–91 | date = Sep 2003 | pmid = 12957674 | doi = 10.1016/S0039-128X(03)00100-4 | s2cid = 6023862 }}

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• {{UCSC genome browser|NR1H3}}
• {{UCSC gene details|NR1H3}}

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{{Transcription factors|g2}}

{{FXR and LXR modulators}}

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Category:Intracellular receptors

Category:Transcription factors