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J. Biol. Chem., Vol. 278, Issue 9, 7709-7717, February 28, 2003
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From the Although many co-activators have been identified
for various nuclear receptors, relatively fewer co-repressors have been
isolated and characterized. Here we report the identification of a
novel testicular orphan nuclear receptor-4 (TR4)-associated protein (TRA16) that is mainly localized in the nucleus of cells as a repressor
to suppress TR4-mediated transactivation. The suppression of
TR4-mediated transactivation is selective because TRA16 shows only a
slight influence on the transactivation of androgen receptor, glucocorticoid receptor, and progesterone receptor. Sequence
analysis shows that TRA16 is a novel gene with 139 amino acids in an
open reading frame with a molecular mass of 16 kDa, which did
not match any published gene sequences. Mammalian two-hybrid system and co-immunoprecipitation assays both demonstrate that TRA16 can interact
strongly with TR4. The electrophoretic mobility shift assay suggests
that TRA16 may suppress TR4-mediated transactivation via decreased
binding between the TR4 protein and the TR4 response element on the
target gene(s). Furthermore, TRA16 can also block the interaction
between TR4 and TR4 ligand-binding domain through interacting
with TR4-DNA-binding and ligand-binding domains. These unique
suppression mechanisms suggest that TRA16 may function as a novel
repressor to selectively suppress the TR4-mediated transactivation.
Identification of a Novel Testicular Orphan
Receptor-4 (TR4)-associated Protein as Repressor for the
Selective Suppression of TR4-mediated Transactivation*
§,
¶,
,
,
, and
George Whipple Laboratory for Cancer
Research Departments of Pathology, Urology, Radiation Oncology, and
Cancer Center, University of Rochester Medical Center, Rochester, New
York 14642, the § Department of Surgery, Beijing Institute
for Cancer Research, Beijing Cancer Hospital, Peking University 100036 Beijing, China, and the ¶ Department of Surgery, First Hospital,
Peking University, 100034, Beijing, China
*
This work was supported by National Institutes of Health
Grant DK56784 and a George Whipple Professorship Endowment.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. E-mail:
chang@urmc.rochester.edu.
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T. Nakajima, S. Fujino, G. Nakanishi, Y.-S. Kim, and A. M. Jetten TIP27: a novel repressor of the nuclear orphan receptor TAK1/TR4 Nucleic Acids Res., August 9, 2004; 32(14): 4194 - 4204. [Abstract] [Full Text] [PDF] |
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