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J. Biol. Chem., Vol. 276, Issue 21, 18007-18017, May 25, 2001
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From the We demonstrate that dexamethasone-mediated
transcription activation of the cytochrome P-450c27 promoter involves a
physical interaction and functional synergy between glucocorticoid
receptor (GR) and Ets2 factor. Ets2 protein binding to a "weak"
Ets-like site of the promoter is dependent on GR bound to the adjacent cryptic glucocorticoid response element. Coimmunoprecipitation and
chemical cross-linking experiments show physical interaction between GR
and Ets2 proteins. Mutational analyses show synergistic effects of Ets2
and GR in dexamethasone-mediated activation of the cytochrome P-450c27
promoter. The DNA-binding domain of GR, lacking the transcription
activation and ligand-binding domains, was fully active in synergistic
activation of the promoter with intact Ets2. The DNA-binding domain of
Ets2 lacking the transcription activation domain showed a dominant
negative effect on the transcription activity. Finally, a fusion
protein consisting of the GR DNA-binding domain and the transcription
activation domain of Ets2 fully supported the transcription activity,
suggesting a novel synergy between the two proteins, which does not
require the transactivation domain of GR. Our results also provide new
insights on the role of putative weak consensus Ets sites in
transcription activation, possibly through synergistic interaction with
other gene-specific transcription activators.
Physical Interaction and Functional Synergy between
Glucocorticoid Receptor and Ets2 Proteins for Transcription Activation
of the Rat Cytochrome P-450c27 Promoter*
,,,§,,,
,, and**
Department of Animal Biology and Mari Lowe
Center for Comparative Oncology, School of Veterinary Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104, ¶ Science Applications International Corporation, Frederick Cancer
Research and Development Center, Frederick, Maryland 21702, and the
Program in Cancer Genetics, Cancer Center, Medical College of
Pennsylvania and Hahnemann University,
Philadelphia, Pennsylvania 19102
*
This work was supported in part by National Institutes of
Health Grants GM34883 and CA22762.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.
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