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Originally published In Press as doi:10.1074/jbc.C200570200 on October 30, 2002

J. Biol. Chem., Vol. 277, Issue 50, 48479-48483, December 13, 2002
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Mutations in the Estrogen Receptor DNA-binding Domain Discriminate between the Classical Mechanism of Action and Cross-talk with Stat5b and Activating Protein 1 (AP-1)*

Linda Björnström and Maria SjöbergDagger

From the Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Estrogen receptors (ERs) efficiently potentiate the transcriptional activity of prolactin-activated Stat5b through a mechanism that involves the ER DNA-binding domain (DBD) and the hinge domain. We have identified residues within the DBD of ER that are critical for the functional interaction of ER with Stat5b. We show that disruption of the second zinc finger structure abrogated cross-talk between ER and Stat5b, while the structure of the first zinc finger was not important. Furthermore, we confirm that intact DNA binding activity was not required for potentiation of Stat5b activity and that the dimerization of ER did not seem to be involved. Ligand-bound ERs also modulated activating protein 1-dependent transcription, and our data demonstrate that both zinc finger structures of the ER DBD are important for an intact response. We show that introduction of various point mutations within the DBD altered the response of the receptor to 17beta -estradiol and to the estrogen antagonists 4-hydroxytamoxifen and ICI 182,870 on the collagenase promoter. These findings provide new insights into the mechanisms by which ERs act in cross-talk with non-related transcription factors.


* This work was supported by the Swedish Cancer Society, the Karolinska Institutet, the Swedish Medical Society, the M. Bergwall Foundation, and the Å. Wiberg Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Karo Bio AB, Novum, SE-141 57 Huddinge, Sweden. Tel.: 46-8-608-6070; Fax: 46-8-774-82-61; E-mail: maria.sjoberg@karobio.se.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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