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.
The Transcriptional Activity of Estrogen Receptor- Is Dependent on Ca2+/Calmodulin*
Lu Li,
Zhigang Li, , and
David B. Sacks
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
Abstract:
Estrogen binds to estrogen receptors in cells, thereby activatingthe receptors and eliciting biological effects. One of the bestcharacterized effects of estrogen receptor- (ER) is transcriptionalactivation that regulates selected target genes in the nucleus.Work from several laboratories has documented a Ca2+-dependentinteraction between ER and calmodulin. In addition, we previouslyshowed that antagonism of calmodulin function in cells preventedestradiol from inducing ER transcriptional activity, suggestingthat association of ER with calmodulin participates in ER function.In this study we adopted a multifaceted approach to directlyaddress this hypothesis. The calmodulin binding domain on ERwas identified and several mutant ER constructs unable to bindcalmodulin were generated. Elimination of calmodulin bindingprevented estradiol from stimulating ER transcriptional activation.Essentially identical results were obtained when intracellularCa2+ was chelated with the cell-permeable chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraaceticacid tetra(acetoxymethyl)ester (BAPTA-AM). Moreover, CaM1234,a calmodulin mutant that is unable to bind Ca2+, functionedas a dominant negative construct. Transfection of cells withCaM1234 reduced estradiol-stimulated ER transcriptional activity.These data indicate that binding to calmodulin is required fornormal transcriptional function of ER.
Received for publication September 15, 2004.
Revision received January 3, 2005.
* This work was supported in part by United States Army GrantDAMD 17-02-1-0305, National Institutes of Health Grant CA93645(to D. B. S.), and a Susan G. Komen Breast Cancer FoundationGrant (to L. L.). The costs of publication of this article weredefrayed in part by the payment of page charges. This articlemust therefore be hereby marked "advertisement" in accordancewith 18 U.S.C. Section 1734 solely to indicate this fact.
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.
The editors suggest the following Related Resources on Science sites:
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.
Is Dependent on Ca2+/Calmodulin
(ER
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: 
