RXR – centralny regulator wielu ścieżek sygnałowych w organizmie

Katarzyna Sołtys; Bartosz Leszczyński; Andrzej Ożyhar

doi:10.2478/ahem-2021-0005

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RXR – centralny regulator wielu ścieżek sygnałowych w organizmie

Postępy Higieny i Medycyny Doświadczalnej

Volume 75 (2021): Issue 1 (January 2021)

By: Katarzyna Sołtys, Bartosz Leszczyński and Andrzej Ożyhar

Open Access

|Oct 2021

Abstract

Nuclear receptors (NRs) are a superfamily of transcription factors that play an important role in regulating many biological processes. The retinoid X receptor (RXR) is unique among NRs because it can form both homodimers and heterodimers with other representatives of the family. RXR modulates the expression of different genes and that is why it could be a good target for many therapies. Dysregulation of RXR signaling leads to various diseases, including neurodegenerative diseases, obesity, diabetes and cancer. Many molecules have been described as potential ligands for RXR. However, only a few of them are currently approved for clinical use. Retinoids play important role in regulation of skin cells growth and differentiation as well as have immunomodulatory and anti-inflammatory effects. Therefore they have found use in treatment of skin lesions and some types of cancers. This review summarizes general information about RXR, its structure, ligands and mechanism of action as well as its potential role in cancer therapy and metabolic syndrome.

References

Sladek F.M.: What are nuclear receptor ligands? Mol. Cell. Endocrinol., 2011; 334: 3-13
Open DOI Search in Google Scholar Back to article
Młynarczuk J., Rękawiecki R.: The role of the orphan receptor SF-1 in the development and function of the ovary. Reprod. Biol., 2010; 10: 177-193
Open DOI Search in Google Scholar Back to article
Sánchez-Martínez R., Castillo A.I., Steinmeyer A., Aranda A.: The retinoid X receptor ligand restores defective signalling by the vitamin D receptor. EMBO Rep., 2006; 7: 1030-1034
Open DOI Search in Google Scholar Back to article
Lefebvre P., Benomar Y., Staels B.: Retinoid X receptors: Common heterodimerization partners with distinct functions. Trends Endocrinol. Metab., 2010; 21: 676-683
Open DOI Search in Google Scholar Back to article
Skerrett R., Malm T., Landreth G.: Nuclear receptors in neurodegenerative diseases. Neurobiol. Dis., 2014; 72: 104-116
Open DOI Search in Google Scholar Back to article
Mangelsdorf D.J., Ong E.S., Dyck J.A., Evans R.M.: Nuclear receptor that identifies a novel retinoic acid response pathway. Nature, 1990; 345: 224-229
Open DOI Search in Google Scholar Back to article
Heyman R.A., Mangelsdorf D.J., Dyck J.A., Stein R.B., Eichele G., Evans R.M., Thaller C.: 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell, 1992; 68: 397-406
Open DOI Search in Google Scholar Back to article
Mangelsdorf D.J., Borgmeyer U., Heyman R.A., Zhou J.Y., Ong E.S., Oro A.E., Kakizuka A., Evans R.M.: Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev., 1992; 6: 329-344
Open DOI Search in Google Scholar Back to article
Rowe A.: Retinoid X receptors. Int. J. Biochem. Cell Biol., 1997; 29: 275-278
Open DOI Search in Google Scholar Back to article
Aranda A., Pascual A.: Nuclear hormone receptors and gene expression. Physiol. Rev., 2001; 81: 1269-1304
Open DOI Search in Google Scholar Back to article
McKenna N.J., O’Malley B.W.: Combinatorial control of gene expression by nuclear receptors and coregulators. Cell, 2002; 108: 465-474
Open DOI Search in Google Scholar Back to article
Hanish B.J., Hackney Price J.F., Kaneko I., Ma N., van der Vaart A., Wagner C.E., Jurutka P.W., Marshall P.A.: A novel gene expression analytics-based approach to structure aided design of rexinoids for development as next-generation cancer therapeutics. Steroids, 2018; 135: 36-49
Open DOI Search in Google Scholar Back to article
Yasmin R., Yeung K.T., Chung R.H., Gaczynska M.E., Osmulski P.A., Noy N.: DNA-looping by RXR tetramers permits transcriptional regulation “at a distance”. J. Mol. Biol., 2004; 343: 327-338
Open DOI Search in Google Scholar Back to article
Shulman A.I., Larson C., Mangelsdorf D.J., Ranganathan R.: Structural determinants of allosteric ligand activation in RXR heterodimers. Cell, 2004; 116: 417-429
Open DOI Search in Google Scholar Back to article
Westin S., Kurokawa R., Nolte R.T., Wisely G.B., McInerney E.M., Rose D.W., Milburn M.V., Rosenfeld M.G., Glass C.K.: Interactions controlling the assembly of nuclear-receptor heterodimers and co-activators. Nature, 1998; 395: 199-202
Open DOI Search in Google Scholar Back to article
Germain P., Iyer J., Zechel C., Gronemeyer H.: Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature, 2002; 415: 187-192
Open DOI Search in Google Scholar Back to article
Zhang X.K., Lehmann J., Hoffmann B., Dawson M.I., Cameron J., Graupner G., Hermann T., Tran P., Pfahl M.: Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature, 1992; 358: 587-591
Open DOI Search in Google Scholar Back to article
Kersten S., Kelleher D., Chambon P., Gronemeyer H., Noy N.: Retinoid X receptor alpha forms tetramers in solution. Proc. Natl. Acad. Sci. USA, 1995; 92: 8645-8649
Open DOI Search in Google Scholar Back to article
Tanaka T., Suh K.S., Lo A.M., De Luca L.M.: p21WAF1/CIP1 is a common transcriptional target of retinoid receptors: Pleiotropic regulatory mechanism through retinoic acid receptor (RAR)/retinoid X receptor (RXR) heterodimer and RXR/RXR homodimer. J. Biol. Chem., 2007; 282: 29987-29997
Open DOI Search in Google Scholar Back to article
Núñez V., Alameda D., Rico D., Mota R., Gonzalo P., Cedenilla M., Fischer T., Boscá L., Glass C.K., Arroyo A.G., Ricote M.: Retinoid X receptor alpha controls innate inflammatory responses through the up-regulation of chemokine expression. Proc. Natl. Acad. Sci. USA, 2010; 107: 10626-10631
Open DOI Search in Google Scholar Back to article
Chen H., Privalsky M.L.: Cooperative formation of high-order oligomers by retinoid X receptors: An unexpected mode of DNA recognition. Proc. Natl. Acad. Sci. USA, 1995; 92: 422-426
Open DOI Search in Google Scholar Back to article
Mark M., Ghyselinck N.B., Chambon P.: Function of retinoid nuclear receptors: Lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu. Rev. Pharmacol. Toxicol., 2006; 46: 451-480
Open DOI Search in Google Scholar Back to article
Chiang J.Y.: Bile acid regulation of gene expression: Roles of nuclear hormone receptors. Endocr. Rev., 2002; 23: 443-463
Open DOI Search in Google Scholar Back to article
Sadasivuni M.K., Reddy B.M., Singh J., Anup M.O., Sunil V., Lakshmi M.N., Yogeshwari S., Chacko S.K., Pooja T.L., Dandu A., Harish C., Gopala A.S., Pratibha S., Naveenkumar B.S., Pallavi P.M. i wsp.: CNX-013-B2, a unique pan tissue acting rexinoid, modulates several nuclear receptors and controls multiple risk factors of the metabolic syndrome without risk of hypertriglyceridemia, hepatomegaly and body weight gain in animal models. Diabetol. Metab. Syndr., 2014; 6: 83
Open DOI Search in Google Scholar Back to article
Széles L., Póliska S., Nagy G., Szatmari I., Szanto A., Pap A., Lindstedt M., Santegoets S.J., Rühl R., Dezsö B., Nagy L.: Research resource: Transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells. Mol. Endocrinol., 2010; 24: 2218-2231
Open DOI Search in Google Scholar Back to article
Kim H.T., Kong G., DeNardo D., Li Y., Uray I., Pal S., Mohsin S., Hilsenbeck S.G., Bissonnette R., Lamph W.W., Johnson K., Brown P.H.: Identification of biomarkers modulated by the rexinoid LGD1069 (Bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res., 2006; 66: 12009-12018
Open DOI Search in Google Scholar Back to article
Prüfer K., Barsony J.: Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor. Mol. Endocrinol., 2002; 16: 1738-1751
Open DOI Search in Google Scholar Back to article
Chambon P.: A decade of molecular biology of retinoic acid receptors. FASEB J., 1996; 10: 940-954
Open DOI Search in Google Scholar Back to article
Rochette-Egly C.: Nuclear receptors: Integration of multiple signalling pathways through phosphorylation. Cell. Signal., 2003; 15: 355-366
Open DOI Search in Google Scholar Back to article
Wärnmark A., Treuter E., Wright A.P., Gustafsson J.A.: Activation functions 1 and 2 of nuclear receptors: Molecular strategies for transcriptional activation. Mol. Endocrinol., 2003; 17: 1901-1909
Open DOI Search in Google Scholar Back to article
Kumar R., Thompson E.B.: Transactivation functions of the Nterminal domains of nuclear hormone receptors: Protein folding and coactivator interactions. Mol. Endocrinol., 2003; 17: 1-10
Open DOI Search in Google Scholar Back to article
Fernandez E.J.: Allosteric pathways in nuclear receptors – Potential targets for drug design. Pharmacol. Ther., 2018; 183: 152-159
Open DOI Search in Google Scholar Back to article
Andersen R.J., Mawji N.R., Wang J., Wang G., Haile S., Myung J.K., Watt K., Tam T., Yang Y.C., Bañuelos C.A., Williams D.E., McEwan I.J., Wang Y., Sadar M.D.: Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the aminoterminus domain of the androgen receptor. Cancer Cell, 2010; 17: 535-546
Open DOI Search in Google Scholar Back to article
Anbalagan M., Huderson B., Murphy L., Rowan B.G.: Post-translational modifications of nuclear receptors and human disease. Nucl. Recept. Signal., 2012; 10: e001
Open DOI Search in Google Scholar Back to article
Ahuja H.S., Szanto A., Nagy L., Davies P.J.: The retinoid X receptor and its ligands: Versatile regulators of metabolic function, cell differentiation and cell death. J. Biol. Regul. Homeost. Agents, 2003; 17: 29-45
Search in Google Scholar Back to article
Egea P.F., Mitschler A., Moras D.: Molecular recognition of agonist ligands by RXRs. Mol. Endocrinol., 2002; 16: 987-997
Open DOI Search in Google Scholar Back to article
Adam-Stitah S., Penna L., Chambon P., Rochette-Egly C.: Hyperphosphorylation of the retinoid X receptor α by activated c-Jun NH2-terminal kinases. J. Biol. Chem., 1999; 274: 18932-18941
Open DOI Search in Google Scholar Back to article
Bastien J., Adam-Stitah S., Plassat J.L., Chambon P., Rochette-Egly C.: The phosphorylation site located in the A region of retinoic X receptor α is required for the antiproliferative effect of retinoic acid (RA) and the activation of RA target genes in F9 cells. J. Biol. Chem., 2002; 277: 28683-28689
Open DOI Search in Google Scholar Back to article
Choi S.J., Chung S.S., Rho E.J., Lee H.W., Lee M.H., Choi H.S., Seol J.H., Baek S.H., Bang O.S., Chung C.H.: Negative modulation of RXRα transcriptional activity by small ubiquitin-related modifier (SUMO) modification and its reversal by SUMO-specific protease SUSP1. J. Biol. Chem., 2006; 281: 30669-30677
Open DOI Search in Google Scholar Back to article
Sołtys K., Ożyhar A.: Ordered structure-forming properties of the intrinsically disordered AB region of hRXRγ and its ability to promote liquid-liquid phase separation. J. Steroid Biochem. Mol. Biol., 2020; 198: 105571
Open DOI Search in Google Scholar Back to article
Alberti S., Gladfelter A., Mittag T.: Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell, 2019; 176: 419-434
Open DOI Search in Google Scholar Back to article
Alberti S., Dormann D.: Liquid-liquid phase separation in disease. Annu. Rev. Genet., 2019; 53: 171-194
Open DOI Search in Google Scholar Back to article
Patel A., Lee H.O., Jawerth L., Maharana S., Jahnel M., Hein M.Y., Stoynov S., Mahamid J., Saha S., Franzmann T.M., Pozniakovski A., Poser I., Maghelli N., Royer L.A., Weigert M. i wsp.: A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell, 2015; 162: 1066-1077
Open DOI Search in Google Scholar Back to article
Boija A., Klein I.A., Sabari B.R., Dall’Agnese A., Coffey E.L., Zamudio A.V., Li C.H., Shrinivas K., Manteiga J.C., Hannett N.M., Abraham B.J., Afeyan L.K., Guo Y.E., Rimel J.K., Fant C.B. i wsp.: Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell, 2018; 175: 1842-1855. e16
Open DOI Search in Google Scholar Back to article
Kumar R., Johnson B.H., Thompson E.B.: Overview of the structural basis for transcription regulation by nuclear hormone receptors. Essays Biochem., 2004; 40: 27-39
Open DOI Search in Google Scholar Back to article
Gronemeyer H., Miturski R.: Molecular mechanisms of retinoid action. Cell. Mol. Biol. Lett., 2001; 6: 3-52
Search in Google Scholar Back to article
Wilson T.E., Paulsen R.E., Padgett K.A., Milbrandt J.: Participation of non-zinc finger residues in DNA binding by two nuclear orphan receptors. Science, 1992; 256: 107-110
Open DOI Search in Google Scholar Back to article
Zechel C., Shen X.Q., Chambon P., Gronemeyer H.: Dimerization interfaces formed between the DNA binding domains determine the cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements. EMBO J., 1994; 13: 1414-1424
Open DOI Search in Google Scholar Back to article
Zechel C., Shen X.Q., Chen J.Y., Chen Z.P., Chambon P., Gronemeyer H.: The dimerization interfaces formed between the DNA binding domains of RXR, RAR and TR determine the binding specificity and polarity of the full-length receptors to direct repeats. EMBO J., 1994; 13: 1425-1433
Open DOI Search in Google Scholar Back to article
Black B.E., Holaska J.M., Rastinejad F., Paschal B.M.: DNA binding domains in diverse nuclear receptors function as nuclear export signals. Curr. Biol., 2001; 11: 1749-1758
Open DOI Search in Google Scholar Back to article
Jacobs C.M., Paulsen R.E.: Crosstalk between ERK2 and RXR regulates nuclear import of transcription factor NGFI-B. Biochem. Biophys. Res. Commun., 2005; 336: 646-652
Open DOI Search in Google Scholar Back to article
Dash A.K., Yende A.S., Jaiswal B., Tyagi R.K.: Heterodimerization of retinoid X receptor with xenobiotic receptor partners occurs in the cytoplasmic compartment: Mechanistic insights of events in living cells. Exp. Cell Res., 2017; 360: 337-346
Open DOI Search in Google Scholar Back to article
García P., Lorenzo P., de Lera A.R.: Natural ligands of RXR receptors. In: Retinoid Signaling Pathways, ed.: E. Pohl. Academic Press, Cambridge MA 2020, 209-234
Open DOI Search in Google Scholar Back to article
Hsieh J.C., Whitfield G.K., Jurutka P.W., Haussler C.A., Thatcher M.L., Thompson P.D., Dang H.T., Galligan M.A., Oza A.K., Haussler M.R.: Two basic amino acids C-terminal of the proximal box specify functional binding of the vitamin D receptor to its rat osteocalcin deoxyribonucleic acid-responsive element. Endocrinology, 2003; 144: 5065-5080
Open DOI Search in Google Scholar Back to article
Kovalevich J., Yen W., Ozdemir A., Langford D.: Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism. J. neuroimmune Pharmacol., 2015; 10: 55-73
Open DOI Search in Google Scholar Back to article
Zomer A.W., van Der Burg B., Jansen G.A., Wanders R.J., Poll-The B.T., van Der Saag P.T.: Pristanic acid and phytanic acid: Naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor α. J. Lipid Res., 2000; 41: 18011807
Open DOI Search in Google Scholar Back to article
de Lera Á.R., Krezel W., Rühl R.: An endogenous mammalian retinoid X receptor ligand, at last! ChemMedChem, 2016; 11: 1027-1037
Open DOI Search in Google Scholar Back to article
Laudet V., Gronemeyer H.: The Nuclear Receptor FactsBook. Academic Press, Cambridge MA 2002
Open DOI Search in Google Scholar Back to article
Bruck N., Bastien J., Bour G., Tarrade A., Plassat J.L., Bauer A., Adam-Stitah S., Rochette-Egly C.: Phosphorylation of the retinoid X receptor at the omega loop, modulates the expression of retinoic-acid-target genes with a promoter context specificity. Cell. Signal., 2005; 17: 1229-1239
Open DOI Search in Google Scholar Back to article
Germain P., Chambon P., Eichele G., Evans R.M., Lazar M.A., Leid M., De Lera A.R., Lotan R., Mangelsdorf D.J., Gronemeyer H.: International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol. Rev., 2006; 58: 760-772
Open DOI Search in Google Scholar Back to article
Bastien J., Rochette-Egly C.: Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene, 2004; 328: 1-16
Open DOI Search in Google Scholar Back to article
de Almeida N.R., Conda-Sheridan M.: A review of the molecular design and biological activities of RXR agonists. Med. Res. Rev., 2019; 39: 1372-1397
Open DOI Search in Google Scholar Back to article
Kojetin D.J., Matta-Camacho E., Hughes T.S., Srinivasan S., Nwachukwu J.C., Cavett V., Nowak J., Chalmers M.J., Marciano D.P., Kamenecka T.M., Shulman A.I., Rance M., Griffin P.R., Bruning J.B., Nettles K.W.: Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. Nat. Commun., 2015; 6: 8013
Open DOI Search in Google Scholar Back to article
Lee H.Y., Suh Y.A., Robinson M.J., Clifford J.L., Hong W.K., Woodgett J.R., Cobb M.H., Mangelsdorf D.J., Kurie J.M.: Stress pathway activation induces phosphorylation of retinoid X receptor. J. Biol. Chem., 2000; 275: 32193-32199
Open DOI Search in Google Scholar Back to article
Cao X., Liu W., Lin F., Li H., Kolluri S.K., Lin B., Han Y.H., Dawson M.I., Zhang X.K.: Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting. Mol. Cell. Biol., 2004; 24: 9705-9725
Open DOI Search in Google Scholar Back to article
Matsushima-Nishiwaki R., Okuno M., Adachi S., Sano T., Akita K., Moriwaki H., Friedman S.L., Kojima S.: Phosphorylation of retinoid X receptor alpha at serine 260 impairs its metabolism and function in human hepatocellular carcinoma. Cancer Res., 2001; 61: 7675-7682
Search in Google Scholar Back to article
Solomon C., White J.H., Kremer R.: Mitogen-activated protein kinase inhibits 1,25-dihydroxyvitamin D³-dependent signal transduction by phosphorylating human retinoid X receptor α. J. Clin. Invest., 1999; 103: 1729-1735
Open DOI Search in Google Scholar Back to article
Glass C.K.: Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr. Rev., 1994; 15: 391-407
Open DOI Search in Google Scholar Back to article
Rosenfeld M.G., Glass C.K.: Coregulator codes of transcriptional regulation by nuclear receptors. J. Biol. Chem., 2001; 276: 3686536868
Open DOI Search in Google Scholar Back to article
Perissi V., Staszewski L.M., McInerney E.M., Kurokawa R., Krones A., Rose D.W., Lambert M.H., Milburn M.V., Glass C.K., Rosenfeld M.G.: Molecular determinants of nuclear receptor-corepressor interaction. Genes Dev., 1999; 13: 3198-3208
Open DOI Search in Google Scholar Back to article
Wolffe A.P., Pruss D.: Targeting chromatin disruption: Transcription regulators that acetylate histones. Cell, 1996; 84: 817-819
Open DOI Search in Google Scholar Back to article
Shulman A.I., Mangelsdorf D.J.: Retinoid X receptor heterodimers in the metabolic syndrome. N. Engl. J. Med., 2005; 353: 604-615
Open DOI Search in Google Scholar Back to article
Heery D.M., Kalkhoven E., Hoare S., Parker M.G.: A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature, 1997; 387: 733-736
Open DOI Search in Google Scholar Back to article
Krężel W., Rühl R., de Lera A.R.: Alternative retinoid X receptor (RXR) ligands. Mol. Cell. Endocrinol., 2019; 491: 110436
Open DOI Search in Google Scholar Back to article
Arnold S.L., Amory J.K., Walsh T.J., Isoherranen N.: A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS. J. Lipid Res., 2012; 53: 587-598
Open DOI Search in Google Scholar Back to article
Cheng C., Michaels J., Scheinfeld N.: Alitretinoin: A comprehensive review. Expert Opin. Investig. Drugs, 2008; 17: 437-443
Open DOI Search in Google Scholar Back to article
de Urquiza A.M., Liu S., Sjöberg M., Zetterström R.H., Griffiths W., Sjövall J., Perlmann T.: Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science, 2000; 290: 2140-2144
Open DOI Search in Google Scholar Back to article
Lengqvist J., Mata De Urquiza A., Bergman A.C., Willson T.M., Sjövall J., Perlmann T., Griffiths W.J.: Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol. Cell. Proteomics, 2004; 3: 692-703
Open DOI Search in Google Scholar Back to article
Mic F.A., Molotkov A., Benbrook D.M., Duester G.: Retinoid activation of retinoic acid receptor but not retinoid X receptor is sufficient to rescue lethal defect in retinoic acid synthesis. Proc. Natl. Acad. Sci. USA, 2003; 100: 7135-7140
Open DOI Search in Google Scholar Back to article
Wallen-Mackenzie A., Mata de Urquiza A., Petersson S., Rodriguez F.J., Friling S., Wagner J., Ordentlich P., Lengqvist J., Heyman R.A., Arenas E., Perlmann T.: Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells. Genes Dev., 2003; 17: 3036-3047
Open DOI Search in Google Scholar Back to article
Wietrzych-Schindler M., Szyszka-Niagolov M., Ohta K., Endo Y., Pérez E., de Lera A.R., Chambon P., Krezel W.: Retinoid X receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol. Psychiatry, 2011; 69: 788-794
Open DOI Search in Google Scholar Back to article
Lo Van A., Sakayori N., Hachem M., Belkouch M., Picq M., Lagarde M., Osumi N., Bernoud-Hubac N.: Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases. Biochimie, 2016; 130: 163-167
Open DOI Search in Google Scholar Back to article
Lemotte P.K., Keidel S., Apfel C.M.: Phytanic acid is a retinoid X receptor ligand. Eur. J. Biochem., 1996; 236: 328-333
Open DOI Search in Google Scholar Back to article
Rühl R., Krzyżosiak A., Niewiadomska-Cimicka A., Rochel N., Széles L., Vaz B., Wietrzych-Schindler M., Álvarez S., Szklenár M., Nagy L., de Lera A.R., Krężel W.: 9-cis-13,14-dihydroretinoic acid is an endogenous retinoid acting as RXR ligand in mice. PLOS Genet., 2015; 11: e1005213
Open DOI Search in Google Scholar Back to article
Harmon M.A., Boehm M.F., Heyman R.A., Mangelsdorf D.J.: Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc. Natl. Acad. Sci. USA, 1995; 92: 61576160
Open DOI Search in Google Scholar Back to article
Hiebl V., Ladurner A., Latkolik S., Dirsch V.M.: Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR. Biotechnol. Adv., 2018; 36: 1657-1698
Open DOI Search in Google Scholar Back to article
Shen D., Yu X., Wu Y., Chen Y., Li G., Cheng F., Xia L.: Emerging roles of bexarotene in the prevention, treatment and anti-drug resistance of cancers. Expert Rev. Anticancer Ther., 2018; 18: 487-499
Open DOI Search in Google Scholar Back to article
Tousi B.: The emerging role of bexarotene in the treatment of Alzheimer’s disease: Current evidence. Neuropsychiatr. Dis. Treat., 2015; 11: 311-315
Open DOI Search in Google Scholar Back to article
Szanto A., Narkar V., Shen Q., Uray I.P., Davies P.J.A., Nagy L.: Retinoid X receptors: X-ploring their (patho)physiological functions. Cell Death Differ., 2004; 11: 126-143
Open DOI Search in Google Scholar Back to article
Wan Y.J., An D., Cai Y., Repa J.J., Hung-Po Chen T., Flores M., Postic C., Magnuson M.A., Chen J., Chien K.R., French S., Mangelsdorf D.J., Sucov H.M.: Hepatocyte-specific mutation establishes retinoid X receptor α as a heterodimeric integrator of multiple physiological processes in the liver. Mol. Cell. Biol., 2000; 20: 4436-4444
Open DOI Search in Google Scholar Back to article
Lu T.T., Repa J.J., Mangelsdorf D.J.: Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J. Biol. Chem., 2001; 276: 37735-37738
Open DOI Search in Google Scholar Back to article
Lu T.T., Makishima M., Repa J.J., Schoonjans K., Kerr T.A., Auwerx J., Mangelsdorf D.J.: Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell, 2000; 6: 507-515
Open DOI Search in Google Scholar Back to article
Repa J.J., Turley S.D., Lobaccaro J.A., Medina J., Li L., Lustig K., Shan B., Heyman R.A., Dietschy J.M., Mangelsdorf D.J.: Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science, 2000; 289: 1524-1529
Open DOI Search in Google Scholar Back to article
Picard F., Auwerx J.: PPARγ and glucose homeostasis. Annu. Rev. Nutr., 2002; 22: 167-197
Open DOI Search in Google Scholar Back to article
Dobrzyn P., Dobrzyn A., Miyazaki M., Cohen P., Asilmaz E., Hardie D.G., Friedman J.M., Ntambi J.M.: Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc. Natl. Acad. Sci. USA, 2004; 101: 6409-6414
Open DOI Search in Google Scholar Back to article
Dziewulska A., Dobosz A.M., Dobrzyn A., Smolinska A., Kolczynska K., Ntambi J.M., Dobrzyn P.: SCD1 regulates the AMPK/ SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle. J. Cell. Physiol., 2020; 235: 1129-1140
Open DOI Search in Google Scholar Back to article
Chang S.C., Rashid A., Gao Y.T., Andreotti G., Shen M.C., Wang B.S., Han T.Q., Zhang B.H., Sakoda L.C., Leitzmann M.F., Chen B.E., Rosenberg P.S., Chen J., Chanock S.J., Hsing A.W.: Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: A population-based case-control study in Shanghai, China. Carcinogenesis, 2008; 29: 944-948
Open DOI Search in Google Scholar Back to article
Wang H., Chu W., Hemphill C., Hasstedt S.J., Elbein S.C.: Mutation screening and association of human retinoid X receptor γ variation with lipid levels in familial type 2 diabetes. Mol. Genet. Metab., 2002; 76: 14-22
Open DOI Search in Google Scholar Back to article
Nohara A., Kawashiri M.A., Claudel T., Mizuno M., Tsuchida M., Takata M., Katsuda S., Miwa K., Inazu A., Kuipers F., Kobayashi J., Koizumi J., Yamagishi M., Mabuchi H.: High frequency of a retinoid X receptor γ gene variant in familial combined hyperlipidemia that associates with atherogenic dyslipidemia. Arterioscler. Thromb. Vasc. Biol., 2007; 27: 923-928
Open DOI Search in Google Scholar Back to article
Shi H., Yu X., Li Q., Ye X., Gao Y., Ma J., Cheng J., Lu Y., Du W., Du J., Ye Q., Zhao X., Zhou L.: Association between PPAR-γ and RXR-α gene polymorphism and metabolic syndrome risk: A case-control study of a Chinese Han population. Arch. Med. Res., 2012; 43: 233-242
Open DOI Search in Google Scholar Back to article
Baldassarro V.A., Krężel W., Fernández M., Schuhbaur B., Giardino L., Calzà L.: The role of nuclear receptors in the differentiation of oligodendrocyte precursor cells derived from fetal and adult neural stem cells. Stem Cell Res., 2019; 37: 101443
Open DOI Search in Google Scholar Back to article
Chiang M.Y., Misner D., Kempermann G., Schikorski T., Giguère V., Sucov H.M., Gage F.H., Stevens C.F., Evans R.M.: An essential role for retinoid receptors RARβ and RXRγ in longterm potentiation and depression. Neuron, 1998; 21: 1353-1361
Open DOI Search in Google Scholar Back to article
Huang J.K., Jarjour A.A., Nait Oumesmar B., Kerninon C., Williams A., Krezel W., Kagechika H., Bauer J., Zhao C., Baron-Van Evercooren A., Chambon P., Ffrench-Constant C., Franklin R.J.: Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat. Neurosci., 2011; 14: 45-53
Open DOI Search in Google Scholar Back to article
Tanaka T., Dancheck B.L., Trifiletti L.C., Birnkrant R.E., Taylor B.J., Garfield S.H., Thorgeirsson U., De Luca L.M.: Altered localization of retinoid X receptor α coincides with loss of retinoid responsiveness in human breast cancer MDA-MB-231 cells. Mol. Cell. Biol., 2004; 24: 3972-3982
Open DOI Search in Google Scholar Back to article
Zhong C., Yang S., Huang J., Cohen M.B., Roy-Burman P.: Aberration in the expression of the retinoid receptor, RXRα, in prostate cancer. Cancer Biol. Ther., 2003; 2: 179-184
Open DOI Search in Google Scholar Back to article
Crowe D.L., Chandraratna R.A.: A retinoid X receptor (RXR)-selective retinoid reveals that RXR-α is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands. Breast Cancer Res., 2004; 6: R546-R555
Open DOI Search in Google Scholar Back to article
Ando N., Shimizu M., Okuno M., Matsushima-Nishiwaki R., Tsurumi H., Tanaka T., Moriwaki H.: Expression of retinoid X receptor alpha is decreased in 3’-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats. Oncol. Rep., 2007; 18: 879-884
Open DOI Search in Google Scholar Back to article
Takiyama Y., Miyokawa N., Sugawara A., Kato S., Ito K., Sato K., Oikawa K., Kobayashi H., Kimura S., Tateno M.: Decreased expression of retinoid X receptor isoforms in human thyroid carcinomas. J. Clin. Endocrinol. Metab., 2004; 89: 5851-5861
Open DOI Search in Google Scholar Back to article
Huang G.L., Zhang W., Ren H.Y., Shen X.Y., Chen Q.X., Shen D.Y.: Retinoid X receptor α enhances human cholangiocarcinoma growth through simultaneous activation of Wnt/β-catenin and nuclear factor-κB pathways. Cancer Sci., 2015; 106: 1515-1523
Open DOI Search in Google Scholar Back to article
Zhu J., Nasr R., Pérès L., Riaucoux-Lormière F., Honoré N., Berthier C., Kamashev D., Zhou J., Vitoux D., Lavau C., de Thé H.: RXR is an essential component of the oncogenic PML/RARA complex in vivo. Cancer Cell, 2007; 12: 23-35
Open DOI Search in Google Scholar Back to article
Zhang X., Zhou H., Su Y.: Targeting truncated RXRα for cancer therapy. Acta Biochim. Biophys. Sin., 2016; 48: 49-59
Open DOI Search in Google Scholar Back to article
Zhou H., Liu W., Su Y., Wei Z., Liu J., Kolluri S.K., Wu H., Cao Y., Chen J., Wu Y., Yan T., Cao X., Gao W., Molotkov A., Jiang F. i wsp.: NSAID sulindac and its analog bind RXRα and inhibit RXRα-dependent AKT signaling. Cancer Cell, 2010; 17: 560-573
Open DOI Search in Google Scholar Back to article