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Originally published In Press as doi:10.1074/jbc.M202311200 on April 4, 2002
J. Biol. Chem., Vol. 277, Issue 24, 22053-22062, June 14, 2002
Structure/Activity Elements of the Multifunctional Protein,
GMEB-1
CHARACTERIZATION OF DOMAINS RELEVANT FOR THE MODULATION OF
GLUCOCORTICOID RECEPTOR TRANSACTIVATION PROPERTIES*
Jun
Chen,
Sunil
Kaul, and
S. Stoney
Simons Jr.
From the Steroid Hormones Section, NIDDK/Laboratory of
Molecular and Cellular Biology, National Institutes of Health,
Bethesda, Maryland 20892
GMEB-1 was initially described as a
component of a 550-kDa heteromeric DNA binding complex that is involved
in the modulation of two properties of glucocorticoid receptor (GR)
transactivation, the dose-response curve of agonists and the partial
agonist activity of antagonists. Subsequently, GMEB-1 was also found to
bind to hsp27, to associate with the coactivator TIF2 in yeast cells, and to participate in Parvovirus replication. To
understand these multiple activities of GMEB-1 at a molecular level, we
have now determined which regions are associated with the various
activities associated with the modulation of GR transactivation
properties. These activities include, homooligomerization,
heterooligomerization, DNA binding, binding to GR and the
transcriptional cofactor CBP, and GR modulation. Complex activities
such as DNA binding and GR modulation, are found to require the
physical combination of those domains that would be predicted from the
involved biochemical processes. We have previously documented that
GMEB-1 possesses both GR modulatory and intrinsic transactivation
activity. However, the domains for these two activities of GMEB-1 are
found not to overlap. This separation of activities provides a
structural basis for our prior biological observations that the
modulation of the dose-response curve and partial agonist activity of
GR complexes is independent of the total levels of gene activation by
the same GR complexes.
*
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: Bldg. 8, Rm. B2A-07,
NIDDK/LMCB, NIH, Bethesda, MD 20892. Tel.: 301-496-6796; Fax:
301-402-3572; E-mail: steroids@helix.nih.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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