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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs*
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Amino Acid Sequence
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Amino Acids, Acidic / genetics
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Amino Acids, Acidic / metabolism
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Glutamine / genetics
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Glutamine / metabolism
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Humans
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Mice
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Molecular Sequence Data
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Proline / genetics
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Proline / metabolism
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Serine / genetics
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Serine / metabolism
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Threonine / genetics
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Threonine / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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AHR protein, human
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Ahr protein, mouse
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Amino Acids, Acidic
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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GAL4 (1-147) protein, S cerevisiae
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Receptors, Aryl Hydrocarbon
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Recombinant Fusion Proteins
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Glutamine
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Threonine
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Serine
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Proline