Reactome | RXRA binds ligands

RXRA binds ligands

Stable Identifier

R-HSA-9843118

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Gene expression (Transcription) (Homo sapiens)

- Epigenetic regulation of gene expression (Homo sapiens)
  - Epigenetic regulation by WDR5-containing histone modifying complexes (Homo sapiens)
    - Epigenetic regulation of gene expression by MLL3 and MLL4 complexes (Homo sapiens)
      - Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes (Homo sapiens)
        
        MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis (Homo sapiens)
        
        RXRA binds ligands (Homo sapiens)

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One of the natural ligands of RXRA (RXRalpha) that can bind to the ligand-binding domain (LBD) of RXRA in the context of the PPARG:RXRA heterodimer is 9-cis-retinoic acid (9cRA) (Heyman et al. 1992, Levin et al. 1992). In the crystalized heterodimer, RXRA was bound to 9cRA, while PPARG was simultaneously bound to one of its synthetic agonists, either rosiglitazone or GI262570 (Gampe et al. 2000). While in vitro the PPARG:RXRA heterodimer can be transcriptionally activated in the presence of only PPARG or RXRA ligands, the presence of ligands for both receptors leads to synergistic activation of PPARG:RXRA heterodimer (Mukherjee et al. 1997). In general, 9cRA is thought to be the main natural ligand of RXRA (Egea et al. 2000). Other candidate natural ligands of RXRA are docosahexaenoic acid (DHA) (de Urquiza et al. 2000, Egea et al. 2002, Lengqvist et al. 2004), and phytanic acid (Lemotte et al. 1996, Kitareewan et al. 1996, Schlüter et al. 2002, Elmazar et al. 2013). For review, please refer to Krezel et al. 2019.

Literature References

PubMed ID	Title	Journal	Year
1310260	9-cis retinoic acid is a high affinity ligand for the retinoid X receptor Heyman, RA, Mangelsdorf, DJ, Dyck, JA, Stein, RB, Eichele, G, Evans, RM, Thaller, C	Cell	1992
15073272	Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain Lengqvist, J, Mata De Urquiza, A, Bergman, AC, Willson, TM, Sjövall, J, Perlmann, T, Griffiths, WJ	Mol Cell Proteomics	2004
11981034	Molecular recognition of agonist ligands by RXRs Egea, PF, Mitschler, A, Moras, D	Mol Endocrinol	2002
10835357	Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid Egea, PF, Mitschler, A, Rochel, N, Ruff, M, Chambon, P, Moras, D	EMBO J	2000
1309942	9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha Levin, AA, Sturzenbecker, LJ, Kazmer, S, Bosakowski, T, Huselton, C, Allenby, G, Speck, J, Kratzeisen, C, Rosenberger, M, Lovey, A	Nature	1992
8617282	Phytanic acid is a retinoid X receptor ligand Lemotte, PK, Keidel, S, Apfel, CM	Eur J Biochem	1996
10882139	Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors Gampe, RT, Montana, VG, Lambert, MH, Miller, AB, Bledsoe, RK, Milburn, MV, Kliewer, SA, Willson, TM, Xu, HE	Mol Cell	2000