Mb. Kumar et al., Differential recruitment of coactivator RIP140 by Ah and estrogen receptors - Absence of a role for LXXL motifs, J BIOL CHEM, 274(32), 1999, pp. 22155-22164
The Ah receptor (AhR), a soluble cytosolic protein, mediates most of the to
xic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related envir
onmental 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 respo
nse elements has yet to be completely understood. The role of coactivator,
RIP140, in the modulation of transcriptional activity of AhR/ARNT heterodim
er was examined. RIP140 enhanced TCDD-mediated, dioxin response element-dri
ven reporter gene activity in three cell lines. Co-immunoprecipitation and
co-localization assays revealed that RIP140 interacted with AhR, but not wi
th ARNT, both in vitro and in cells. Mapping of the interaction sites revea
led that RIP140 was recruited by the AhR transactivation domain via the Q-r
ich 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, wh
ich 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 coactiva
tor pool. In addition, the data suggest that there are distinct motif(s) fo
r the recruitment of RIP140 to AhR and possibly other non-steroid receptors
/transcription factors.