Gene/Protein
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Activating signal cointegrator 1
(
ASC-1
) harbors an autonomous transactivation domain that contains a putative zinc finger motif which provides binding sites for basal transcription factors TBP and TFIIA, transcription integrators steroid receptor coactivator 1 (SRC-1) and CBP-p300, and nuclear receptors, as demonstrated by the
glutathione S-transferase
pull-down assays and the yeast two-hybrid tests. The
ASC-1
binding sites involve the hinge domain but not the C-terminal AF2 core domain of nuclear receptors. Nonetheless,
ASC-1
appears to require the AF2-dependent factors to function (i.e., CBP-p300 and SRC-1), as suggested by the ability of
ASC-1
to coactivate nuclear receptors, either alone or in cooperation with SRC-1 and p300, as well as its inability to coactivate a mutant receptor lacking the AF2 core domain. By using indirect immunofluorescence, we further show that
ASC-1
, a nuclear protein, is localized to the cytoplasm under conditions of serum deprivation but is retained in the nucleus when it is serum starved in the presence of ligand or coexpressed CBP or SRC-1. These results suggest that
ASC-1
is a novel coactivator molecule of nuclear receptors which functions in conjunction with CBP-p300 and SRC-1 and may play an important role in establishing distinct coactivator complexes under different cellular conditions.
...
PMID:Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation. 1045 79
Activating signal cointegrator 1
(
ASC-1
) has been recently reported as a coactivator of some nuclear receptors. In the present study, we have analyzed the expression of
ASC-1
in the mouse testis and investigated its capacity to modulate the transcriptional activity of androgen receptor (AR). We found that although
ASC-1
mRNA was ubiquitously expressed at a low level in mouse tissues, a couple of testis-specific mRNAs were expressed in the adult testis. Cloning of one testis-specific variant revealed that the ubiquitous and testis-specific transcripts of
ASC-1
share at least the same open reading frame. The expression of the testis-specific
ASC-1
mRNAs was developmentally regulated, and the onset of their expression coincided with the initiation of spermatogenesis. In situ hybridization of mouse testis with
ASC-1
antisense probe demonstrated predominant expression of
ASC-1
in the interstitial Leydig cells that express AR. Moreover, yeast two-hybrid tests and
glutathione S-transferase
pull-down assays revealed that
ASC-1
associates directly with AR and that the hinge domain of AR and a putative zinc-finger motif of
ASC-1
are major determinants for their interaction. Transient transfection assays performed by expressing
ASC-1
in combination with AR and an androgen-responsive reporter gene showed that
ASC-1
moderately alters the induction of the reporter gene. Taken together, these results suggest that
ASC-1
may function as an AR coregulator and have a role in testicular functions.
...
PMID:Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor. 1239 Aug 91
