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J. Biol. Chem., Vol. 277, Issue 50, 48479-48483, December 13, 2002
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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 17
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)*
-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.
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.
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