当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1.

Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1.

Abstract：

:Estrogen signaling occurs through at least two distinct molecular pathways: (i) direct binding of liganded estrogen receptors (ERs) to estrogen-responsive DNA elements (EREs) (the "ER/ERE pathway") and (ii) indirect recruitment of liganded ERs to activating protein-1 (AP-1)-responsive DNA elements via heterodimers of Fos and Jun (the "ER/AP-1 pathway"). We have developed a biochemical assay for examining ligand-regulated transcription by ERs in the ER/AP-1 pathway. This assay recapitulates the altered (i.e., agonistic) pharmacology of selective estrogen receptor modulator drugs in this pathway reported previously by using various cell-based assays. We used our biochemical assay to examine the detailed mechanisms of ER/AP-1-dependent transcription. Our studies indicate that (i) ERalpha/AP-1 complexes play a critical role in promoting the formation of stable RNA polymerase II preinitiation complexes leading to transcription initiation, (ii) chromatin is a key determinant of estrogen and selective estrogen receptor modulator signaling in the ERalpha/AP-1 pathway, (iii) distinct domains of ERalpha are required for recruitment to DNA-bound Fos/Jun heterodimers and transcriptional activation at AP-1 sites, and (iv) different enhancer/activator combinations in the ERalpha and AP-1 pathways use coactivators in distinct ways. These studies have increased our understanding of the molecular mechanisms underlying ligand-dependent signaling in the ER/AP-1 pathway and demonstrate the usefulness of this biochemical approach.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Cheung E,Acevedo ML,Cole PA,Kraus WL

doi

10.1073/pnas.0407113102

keywords:

subject

Has Abstract

pub_date

2005-01-18 00:00:00

pages

559-64

issue

3

eissn

0027-8424

issn

1091-6490

pii

0407113102

journal_volume

102

pub_type

杂志文章

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