The mouse and human Ah receptor differ in recognition of LXXLL motifs. Journal   Archives of biochemistry and biophysics. Citation   Arch Biochem Biophys. 471(2):215-23 Publication date   2008 Mar 15 Authors   Flaveny C Reen RK Kusnadi A Perdew GH Investigators   Gary Perdew Grants   United States NIEHS ES011834 United States NIEHS ES04869 United States NIEHS R01 ES004869-20 MeSH headings   Amino Acid Motifs Receptors, Aryl Hydrocarbon MeSH qualifiers   metabolism Abstract   The aryl hydrocarbon receptor (AhR) is a ligand inducible transcription factor that exhibits interspecies differences, with the human and mouse AhR C-terminal transactivation domain sharing only 58% amino acid sequence identity. The AhR has a transactivation domain comprised of proline/serine/threonine-rich, glutamine-rich, and acidic amino acid subdomains. A truncated mAhR and hAhR containing only the acidic subdomain displayed widely differing transactivation potentials. Whether the glutamine-rich subdomain of the mouse AhR and the human AhR differentially recruit LXXLL-motif coactivators was investigated. Transiently expressed GAL4 DNA binding domain (GAL4DBD)-LXXLL-motif fusion proteins were used to map the critical LXXLL binding sequence of the hAhR to amino acid residues 663-688. Several LXXLL-motif GAL4DBD fusion proteins dramatically differed in their ability to influence the transactivation potential of the mAhR and hAhR. These findings suggest that the human and mouse AhR may display differential recruitment of coactivators and hence may exhibit divergent regulation of target genes.