Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3 (nuclear receptor subfamily 3, group B, member 3), is a nuclear receptor that in humans is encoded by the ESRRG (EStrogen Related Receptor Gamma) gene.[1][2][3] It behaves as a constitutive activator of transcription.[4]
This protein is a member of nuclear hormone receptor family of steroid hormone receptors. No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG.[5] It also seems to be the target of bisphenol A (see below).
Bisphenol A binding
There is evidence that bisphenol A functions as an endocrine disruptor by binding strongly to ERR-γ.[4] BPA as well as its nitrated and chlorinated metabolites seems to binds strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER).,[4][6] BPA binding to ERR-γ preserves its basal constitutive activity.[4] It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.[4]
Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta, explaining reports of high bisphenol A accumulation there.[7]
References
- ^ "Entrez Gene: ESRRG estrogen-related receptor gamma".
- ^ Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J (June 1998). "Isolation of a gene encoding a novel member of the nuclear receptor superfamily from the critical region of Usher syndrome type IIa at 1q41". Genomics 50 (3): 382–4. doi:10.1006/geno.1998.5345. PMID 9676434.
- ^ Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT (March 1999). "Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR". Gene 228 (1–2): 101–9. doi:10.1016/S0378-1119(98)00619-2. PMID 10072763.
- ^ a b c d e Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (October 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". J. Biochem. 142 (4): 517–24. doi:10.1093/jb/mvm158. PMID 17761695.
- ^ Huppunen J, Aarnisalo P (February 2004). "Dimerization modulates the activity of the orphan nuclear receptor ERRgamma". Biochem. Biophys. Res. Commun. 314 (4): 964–70. doi:10.1016/j.bbrc.2003.12.194. PMID 14751226.
- ^ Babu S, Vellore NA et al. (2012). "Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma". Biochem. biophys res comm 426 (2): 215–220. doi:10.1016/j.bbrc.2012.08.065. PMID 22935422.
- ^ Takeda Y, Liu X, Sumiyoshi M, Matsushima A, Shimohigashi M, Shimohigashi Y (July 2009). "Placenta expressing the greatest quantity of bisphenol A receptor ER-γ among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform". J. Biochem. 146 (1): 113–22. doi:10.1093/jb/mvp049. PMID 19304792.
External links
- "Master protein found to enhance both muscles and the brain". KurzweilAI. April 7, 2015. Retrieved March 2015.
Further reading
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Nagase T, Ishikawa K, Suyama M et al. (1999). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
- Hong H, Yang L, Stallcup MR (1999). "Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3". J. Biol. Chem. 274 (32): 22618–26. doi:10.1074/jbc.274.32.22618. PMID 10428842.
- Heard DJ, Norby PL, Holloway J, Vissing H (2000). "Human ERRgamma, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: tissue-specific isoforms are expressed during development and in the adult". Mol. Endocrinol. 14 (3): 382–92. doi:10.1210/me.14.3.382. PMID 10707956.
- Greschik H, Wurtz JM, Sanglier S et al. (2002). "Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3". Mol. Cell 9 (2): 303–13. doi:10.1016/S1097-2765(02)00444-6. PMID 11864604.
- Wistow G, Bernstein SL, Wyatt MK et al. (2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Mol. Vis. 8: 205–20. PMID 12107410.
- Hentschke M, Süsens U, Borgmeyer U (2002). "Domains of ERRgamma that mediate homodimerization and interaction with factors stimulating DNA binding". Eur. J. Biochem. 269 (16): 4086–97. doi:10.1046/j.1432-1033.2002.03102.x. PMID 12180985.
- Hentschke M, Süsens U, Borgmeyer U (2003). "PGC-1 and PERC, coactivators of the estrogen receptor-related receptor gamma". Biochem. Biophys. Res. Commun. 299 (5): 872–9. doi:10.1016/S0006-291X(02)02753-5. PMID 12470660.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Hentschke M, Schulze C, Süsens U, Borgmeyer U (2003). "Characterization of calmodulin binding to the orphan nuclear receptor Errgamma". Biol. Chem. 384 (3): 473–82. doi:10.1515/BC.2003.053. PMID 12715898.
- Hentschke M, Borgmeyer U (2004). "Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma". Biochem. Biophys. Res. Commun. 312 (4): 975–82. doi:10.1016/j.bbrc.2003.11.025. PMID 14651967.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Cheung CP, Yu S, Wong KB et al. (2005). "Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues". J. Clin. Endocrinol. Metab. 90 (3): 1830–44. doi:10.1210/jc.2004-1421. PMID 15598686.
- Liu D, Zhang Z, Teng CT (2005). "Estrogen-related receptor-gamma and peroxisome proliferator-activated receptor-gamma coactivator-1alpha regulate estrogen-related receptor-alpha gene expression via a conserved multi-hormone response element". J. Mol. Endocrinol. 34 (2): 473–87. doi:10.1677/jme.1.01586. PMID 15821111.
- Gao M, Sun P, Wang J et al. (2006). "Expression of estrogen receptor-related receptor isoforms and clinical significance in endometrial adenocarcinoma". Int. J. Gynecol. Cancer 16 (2): 827–33. doi:10.1111/j.1525-1438.2006.00527.x. PMID 16681769.
- Gregory SG, Barlow KF, McLay KE et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature 441 (7091): 315–21. doi:10.1038/nature04727. PMID 16710414.
- Wang L, Zuercher WJ, Consler TG et al. (2007). "X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation". J. Biol. Chem. 281 (49): 37773–81. doi:10.1074/jbc.M608410200. PMID 16990259.
- Babu S, Vellore NA et al. (2012). "Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma". Biochem. biophys res comm 426 (2): 215–220. doi:10.1016/j.bbrc.2012.08.065. PMID 22935422.
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