The mouse and human Ah receptor differ in recognition of LXXLL motifs.
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.
Flaveny
Colin
C
Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 309A Life Sciences Building, University Park, PA 16802, USA.
Reen
Rashmeet K
RK
Kusnadi
Ann
A
Perdew
Gary H
GH
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011392:Proline / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D024342:Amino Acids, Acidic; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005973:Glutamine; D011392:Proline; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D013912:Threonine; D014157:Transcription Factors; C111235:AHR protein, human; C484722:Ahr protein, mouse; C064255:GAL4 (1-147) protein, S cerevisiae