Estrogen receptors alpha and beta form heterodimers on DNA
- PMID: 9242648
- DOI: 10.1074/jbc.272.32.19858
Estrogen receptors alpha and beta form heterodimers on DNA
Abstract
The estrogen receptor (ER) is expressed in two forms, ERalpha and ERbeta. Here we show that ERalpha and ERbeta, expressed both in vitro and in vivo, form heterodimers which bind to DNA with an affinity (Kd of approximately 2 nM) similar to that of ERalpha and greater than that of ERbeta homodimers. Mutation analysis of the hormone binding domain of ERalpha suggests that the dimerization interface required to form heterodimers with ERbeta is very similar but not identical to that required for homodimer formation. The heterodimer, like the homodimers, are capable of binding the steroid receptor coactivator-1 when bound to DNA and stimulating transcription of a reporter gene in transfected cells. Given the relative expression of ERalpha and ERbeta in tissues and the difference in DNA binding activity between ERalpha/ERbeta heterodimers and ERbeta it seems likely that the heterodimer is functionally active in a subset of target cells.
Similar articles
-
Dominant activity of activation function 1 (AF-1) and differential stoichiometric requirements for AF-1 and -2 in the estrogen receptor alpha-beta heterodimeric complex.Mol Cell Biol. 1999 Mar;19(3):1919-27. doi: 10.1128/MCB.19.3.1919. Mol Cell Biol. 1999. PMID: 10022879 Free PMC article.
-
Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) alpha and ERbeta.J Biol Chem. 2000 Nov 17;275(46):35986-93. doi: 10.1074/jbc.M006777200. J Biol Chem. 2000. PMID: 10964929
-
Mutual antagonism of estrogen receptors alpha and beta and their preferred interactions with steroid receptor coactivators in human osteoblastic cell lines.J Endocrinol. 2003 Mar;176(3):349-57. doi: 10.1677/joe.0.1760349. J Endocrinol. 2003. PMID: 12630920
-
Estrogen signaling: a subtle balance between ER alpha and ER beta.Mol Interv. 2003 Aug;3(5):281-92. doi: 10.1124/mi.3.5.281. Mol Interv. 2003. PMID: 14993442 Review.
-
Molecular action of the estrogen receptor and hormone dependency in breast cancer.Breast Cancer. 2003;10(2):89-96. doi: 10.1007/BF02967632. Breast Cancer. 2003. PMID: 12736560 Review.
Cited by
-
Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells.J Steroid Biochem Mol Biol. 2016 Jul;161:73-83. doi: 10.1016/j.jsbmb.2015.07.018. Epub 2015 Aug 13. J Steroid Biochem Mol Biol. 2016. PMID: 26277097 Free PMC article. Review.
-
Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways.Mol Cell Biol. 2004 Sep;24(17):7681-94. doi: 10.1128/MCB.24.17.7681-7694.2004. Mol Cell Biol. 2004. PMID: 15314175 Free PMC article.
-
The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-kappa B transcriptional activity in models of rheumatoid arthritis.Arthritis Res Ther. 2005;7(3):R427-38. doi: 10.1186/ar1692. Epub 2005 Feb 21. Arthritis Res Ther. 2005. PMID: 15899029 Free PMC article.
-
Estrogen receptors inhibit Smad3 transcriptional activity through Ap-1 transcription factors.Mol Cell Biochem. 2007 Dec;306(1-2):33-42. doi: 10.1007/s11010-007-9551-1. Epub 2007 Jul 28. Mol Cell Biochem. 2007. PMID: 17660955
-
The role of AEBP1 in sex-specific diet-induced obesity.Mol Med. 2005 Jan-Dec;11(1-12):39-47. doi: 10.2119/2005-00021.Ro. Mol Med. 2005. PMID: 16307171 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
