Nuclear receptor coactivator SRC-1 interacts with the Q-rich subdomain of the AhR and modulates its transactivation potential

Mohan B. Kumar, Gary H. Perdew

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


The aryl hydrocarbon receptor (AhR), a soluble cytosolic protein, mediates many of the toxic effects of TCDD and related chemicals. The toxic effects are largely cell, tissue, and promoter context dependent. Although many details of the overall dioxin signal transduction have been elucidated, the transcriptional regulation of dioxin-induced genes like cyp1A1 is not yet completely understood. Previously, we have shown that the co-regulator RIP140 is a potential AhR coactivator. In this report, the role of coactivator, SRC-1, in AhR-mediated transcriptional regulation was examined. SRC-1 increased AhR-mediated, TCDD-dependent reporter gene activity three-fold in Hepa-1 and COS-1 cells. In in vitro interaction assays, SRC-1 was found to interact with AhR but not with ARNT. SRC-1 interacted weakly with AhR in the absence of TCDD and the addition of ligand further increased SRC-1 binding to AhR. Deletional mapping studies of the AhR revealed that SRC-1 binds to the AhR transactivation domain. Finer mapping of the SRC-1-interacting subdomains in the AhR transactivation domain suggested that the Q-rich subdomain was necessary and sufficient for interaction, similar to that seen with RIP140. Using GFP-tagged constructs, SRC-1 was shown to interact with AhR in cells. Unlike RIP140, LXXLL motifs in SRC-1 were necessary for interaction with AhR in vitro and for coactivation in Hepa-1 cells. The recruitment of certain coactivators by a variety of receptors suggests possible common coactivator pools and competition among receptors for limiting coactivators. Examination of the role of SRC-1 in AhR/ARNT transactivation in ARNT-deficient mutant Hepa-1 c4 cells demonstrates that the AhR transactivation domain is sufficient for enhanced coactivation mediated by SRC-1 in the presence of a transactivation domain deleted ARNT protein.

Original languageEnglish (US)
Pages (from-to)273-286
Number of pages14
JournalGene expression
Issue number5-6
StatePublished - 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics


Dive into the research topics of 'Nuclear receptor coactivator SRC-1 interacts with the Q-rich subdomain of the AhR and modulates its transactivation potential'. Together they form a unique fingerprint.

Cite this