Retinoic acid receptor

From Proteopedia

Revision as of 09:27, 12 January 2023

spinqualitylabelsall models Structure of human retinoic acid receptor γ ligand-binding domain complex with all-trans retinoic acid (PDB entry 2lbd) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights 5 3D structures of retinoic acid receptor Function Retinoic acid receptor (RAR) is a nuclear receptor activated by all-trans and 9-cis retinoic acid. RAR makes a heterodimer with retinoid X receptor (RXR). In the absence of ligand, the RAR/RXR complex binds the hormone response elements complexed with corepressor protein. Upon binding of the ligand, the corepressor disassociates from the receptor and associates with the coactivator leading to transcription activation. RAR contains a DNA-binding domain (DBD) and ligand-binding domain (LBD). There are 3 classes of RAR: α, β and γ. RARα plays an important role in mediating all-transretinoic acid signals[1]. RARβ is a potent inhibitor of breast cancer cells in vitro[2]. RARγ interacts with nuclear receptor co-repressor 1. See details of RAR/RXR complex in RA Mediated T-reg Differentiation. See also Intracellular receptors Relevance RARα is associated with tamoxifen resistance in breast cancer cells[3]. RARβ is a prognostic indicator in stage I non-small-cell lung cancer[4]. Disease RAR and RXR are important in a number of tumor cell models[5]. Structural highlights The .[6] 3D structures of retinoic acid receptor Retinoic acid receptor 3D structures

References

1. ↑ Wu Q, Lin XF, Ye XF, Zhang B, Xie Z, Su WJ. Ubiquitinated or sumoylated retinoic acid receptor alpha determines its characteristic and interacting model with retinoid X receptor alpha in gastric and breast cancer cells. J Mol Endocrinol. 2004 Jun;32(3):595-613. PMID:15171703
2. ↑ Sommer KM, Chen LI, Treuting PM, Smith LT, Swisshelm K. Elevated retinoic acid receptor beta(4) protein in human breast tumor cells with nuclear and cytoplasmic localization. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8651-6. PMID:10411930
3. ↑ Johansson HJ, Sanchez BC, Mundt F, Forshed J, Kovacs A, Panizza E, Hultin-Rosenberg L, Lundgren B, Martens U, Mathe G, Yakhini Z, Helou K, Krawiec K, Kanter L, Hjerpe A, Stal O, Linderholm BK, Lehtio J. Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer. Nat Commun. 2013;4:2175. doi: 10.1038/ncomms3175. PMID:23868472 doi:http://dx.doi.org/10.1038/ncomms3175
4. ↑ Khuri FR, Lotan R, Kemp BL, Lippman SM, Wu H, Feng L, Lee JJ, Cooksley CS, Parr B, Chang E, Walsh GL, Lee JS, Hong WK, Xu XC. Retinoic acid receptor-beta as a prognostic indicator in stage I non-small-cell lung cancer. J Clin Oncol. 2000 Aug;18(15):2798-804. PMID:10920126
5. ↑ Soprano KJ, Soprano DR. Retinoic acid receptors and cancer. J Nutr. 2002 Dec;132(12):3809S-3813S. PMID:12468629
6. ↑ Renaud JP, Rochel N, Ruff M, Vivat V, Chambon P, Gronemeyer H, Moras D. Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid. Nature. 1995 Dec 14;378(6558):681-9. PMID:7501014 doi:http://dx.doi.org/10.1038/378681a0