Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 280 (13): 13097-13104

© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

The Transcriptional Activity of Estrogen Receptor-α Is Dependent on Ca2+/Calmodulin*

Lu Li, Zhigang Li, , and David B. Sacks{ddagger}

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

Abstract: Estrogen binds to estrogen receptors in cells, thereby activating the receptors and eliciting biological effects. One of the best characterized effects of estrogen receptor-α (ERα) is transcriptional activation that regulates selected target genes in the nucleus. Work from several laboratories has documented a Ca2+-dependent interaction between ERα and calmodulin. In addition, we previously showed that antagonism of calmodulin function in cells prevented estradiol from inducing ERα transcriptional activity, suggesting that association of ERα with calmodulin participates in ERα function. In this study we adopted a multifaceted approach to directly address this hypothesis. The calmodulin binding domain on ERα was identified and several mutant ERα constructs unable to bind calmodulin were generated. Elimination of calmodulin binding prevented estradiol from stimulating ERα transcriptional activation. Essentially identical results were obtained when intracellular Ca2+ was chelated with the cell-permeable chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM). Moreover, CaM1234, a calmodulin mutant that is unable to bind Ca2+, functioned as a dominant negative construct. Transfection of cells with CaM1234 reduced estradiol-stimulated ERα transcriptional activity. These data indicate that binding to calmodulin is required for normal transcriptional function of ERα.


Received for publication September 15, 2004. Revision received January 3, 2005.

{ddagger} To whom correspondence should be addressed: Brigham and Women's Hospital, Thorn 530, 75 Francis St., Boston, MA 02115. Tel.: 617-732-6627; Fax: 617-278-6921; E-mail: dsacks{at}rics.bwh.harvard.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
IQGAP1 Binds to Estrogen Receptor-{alpha} and Modulates Its Function.
H. H. Erdemir, Z. Li, and D. B. Sacks (2014)
J. Biol. Chem. 289, 9100-9112
   Abstract »    Full Text »    PDF »
Structural Basis for Ca2+-induced Activation and Dimerization of Estrogen Receptor {alpha} by Calmodulin.
Y. Zhang, Z. Li, D. B. Sacks, and J. B. Ames (2012)
J. Biol. Chem. 287, 9336-9344
   Abstract »    Full Text »    PDF »
IQGAP1 Protein Binds Human Epidermal Growth Factor Receptor 2 (HER2) and Modulates Trastuzumab Resistance.
C. D. White, Z. Li, D. A. Dillon, and D. B. Sacks (2011)
J. Biol. Chem. 286, 29734-29747
   Abstract »    Full Text »    PDF »
Intra- and Interdomain Effects Due to Mutation of Calcium-binding Sites in Calmodulin.
L.-W. Xiong, Q. K. Kleerekoper, X. Wang, and J. A. Putkey (2010)
J. Biol. Chem. 285, 8094-8103
   Abstract »    Full Text »    PDF »
Actin Pedestal Formation by Enteropathogenic Escherichia coli Is Regulated by IQGAP1, Calcium, and Calmodulin.
M. D. Brown, L. Bry, Z. Li, and D. B. Sacks (2008)
J. Biol. Chem. 283, 35212-35222
   Abstract »    Full Text »    PDF »
IQGAP1 modulates activation of B-Raf.
J.-G. Ren, Z. Li, and D. B. Sacks (2007)
PNAS 104, 10465-10469
   Abstract »    Full Text »    PDF »
Induction of Estrogen Receptor {alpha} Expression with Decoy Oligonucleotide Targeted to NFATc1 Binding Sites in Osteoblasts.
L. Penolazzi, M. Zennaro, E. Lambertini, E. Tavanti, E. Torreggiani, R. Gambari, and R. Piva (2007)
Mol. Pharmacol. 71, 1457-1462
   Abstract »    Full Text »    PDF »
Tuberin Nuclear Localization Can Be Regulated by Phosphorylation of Its Carboxyl Terminus.
B. York, D. Lou, and D. J. Noonan (2006)
Mol. Cancer Res. 4, 885-897
   Abstract »    Full Text »    PDF »
Expression Profiling of Endocrine-Disrupting Compounds Using a Customized Cyprinus carpio cDNA Microarray.
L. N. Moens, K. van der Ven, P. Van Remortel, J. Del-Favero, and W. M. De Coen (2006)
Toxicol. Sci. 93, 298-310
   Abstract »    Full Text »    PDF »
E6AP and Calmodulin Reciprocally Regulate Estrogen Receptor Stability.
L. Li, Z. Li, P. M. Howley, and D. B. Sacks (2006)
J. Biol. Chem. 281, 1978-1985
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882