Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs

Mohan B. Kumar, Rex W. Tarpey, Gary H. Perdew

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22155-22164
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number32
DOIs
StatePublished - Aug 6 1999

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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