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J. Biol. Chem., Vol. 277, Issue 10, 8004-8011, March 8, 2002
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From the INSERM EMI-U 9928, 4 rue Larrey, CHU Angers, Angers
Cedex 49033, France and the § Department of
Biochemistry, University of Leicester, University Rd.,
Leicester LE1 7RH, United Kingdom
Signal transducer and activator of transcription
3 (STAT3) transcription factors are cytoplasmic proteins that induce
gene activation in response to cytokine receptor stimulation. Following tyrosine phosphorylation, STAT3 proteins dimerize, translocate to the
nucleus, and activate specific target genes. This transcriptional activation by STAT3 proteins has been shown to require the recruitment of coactivators such as CREB-binding protein (CBP)/p300. In the present
study, we show that steroid receptor coactivator 1, NcoA/SRC1a, originally identified as a nuclear receptor coactivator, also functions
as a coactivator of STAT3 proteins. In coimmunoprecipitations, NcoA/SRC1a was found to associate with STAT3 following IL-6 stimulation of HepG2 hepatoma cells. Pull-down experiments indicated that the
N-terminal part of NcoA/SRC1a associates with the activation domain of
STAT3. Overexpression of NcoA/SRC1a or its SRC1e isoform enhanced
transcriptional activation by STAT3 proteins in transient transfection
experiments. This ability of NcoA/SRC1a to enhance STAT3 activity is
dependent upon the presence of the CBP-interacting domain, activation
domain 1. Using chromatin immunoprecipitation assays, we
found that STAT3, NcoA/SRC1a, and CBP/p300 are simultaneously recruited
to the p21waf1 promoter following interleukin-6 stimulation.
Taken together, these data suggest that CBP/p300 and NcoA/SRC1a may
function in a common pathway to regulate STAT3 transcriptional activity.
Functional Interaction of STAT3 Transcription Factor with the
Coactivator NcoA/SRC1a*
*
This work was supported by a fellowship (to S. G.) from the
Ministere de la Recherche et de la Technologie and by a fellowship (to
F. B.) and a grant from the Ligue Nationale Pour la Recherche Sur le
Cancer as an "Equipe Labelisée La Ligue Contre le Cancer."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. Tel.: 33-2-41-35-47- 33; Fax: 33-2-41-73-16-30; E-mail:
olivier.coqueret@univ-angers.fr.
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