Molecular and Cellular Biology, September 1999, p. 6323-6332, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Center for Ligand and
Transcription1 and Hormone Research
Center,
Received 20 October 1998/Returned for modification 14 December
1998/Accepted 14 June 1999
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.
*
Corresponding author. Mailing address: Center for
Ligand and Transcription, Chonnam National University, Kwangju
500-757, Korea. Phone: 82-62-530-0910. Fax: 82-62-530-0772. E-mail: jlee{at}chonnam.chonnam.ac.kr.
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