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J Biol Chem, Vol. 274, Issue 32, 22155-22164, August 6, 1999
From the § Graduate Program in Biochemistry and
Molecular Biology, the The Ah receptor (AhR), a soluble
cytosolic protein, mediates most of the toxic effects of
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
environmental contaminants. The mechanism of ligand-mediated AhR
activation has been, in part, elucidated. The sequence of events
following the binding of the AhR/AhR nuclear translocator protein
(ARNT) heterodimer to dioxin response elements has yet to be completely
understood. The role of coactivator, RIP140, in the modulation of
transcriptional activity of AhR/ARNT heterodimer was examined. RIP140
enhanced TCDD-mediated, dioxin response element-driven reporter gene
activity in three cell lines. Co-immunoprecipitation and
co-localization assays revealed that RIP140 interacted with AhR, but
not with ARNT, both in vitro and in cells. Mapping of the
interaction sites revealed that RIP140 was recruited by the AhR
transactivation domain via the Q-rich subdomain. The RIP140 domain that
interacts with the AhR was mapped to a location between amino acid
residues 154 and 350, which is distinct from those involved in estrogen
receptor binding. The signature motif, LXXLL, which is
responsible for binding of several coactivators to nuclear receptors,
is not required for RIP140 binding to AhR. These results demonstrate
that the AhR recruits coactivators that are capable of enhancing
transcription and, thus, the AhR may compete with steroid receptors for
a common coactivator pool. In addition, the data suggest that there are distinct motif(s) for the recruitment of RIP140 to AhR and possibly other non-steroid receptors/transcription factors.
Differential Recruitment of Coactivator RIP140 by
Ah and Estrogen Receptors
ABSENCE OF A ROLE FOR LXXLL MOTIFS
§,
, and
¶
Center for Molecular
Toxicology, and the ¶ Department of Veterinary Science,
Pennsylvania State University,
University Park, Pennsylvania 16802
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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