A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

To identify new proteins involved in dioxin-dependent signal transduction and transcriptional regulation, we used a yeast two-hybrid system to identify proteins that interact with the Ah receptor (AhR). We cloned a mouse cDNA, which encodes a novel approximately 37-kDa protein that binds to AhR; we have designated the protein as ...
Ah receptor-interacting protein (AIP). The amino acid sequence of mouse AIP exhibits homology with members of the FK506-binding protein family. AIP also contains three tetratricopeptide repeat (TPR) motifs; the TPR sequence is present in proteins required for cell cycle control and RNA synthesis and in steroid receptor-binding immunophilins. Coimmunoprecipitation experiments in mouse hepatoma cells reveal that AIP is cytoplasmic and associates with unliganded Ah receptor and with hsp90; 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment disrupts the AhR-AIP-hsp90 interaction. Overexpression of AIP augments the response of the CYP1A1 gene to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Our data suggest that AIP influences ligand receptivity and/or nuclear targeting of AhR.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cloning, Molecular, Cytochrome P-450 CYP1A1, Enzyme Induction, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Liver Neoplasms, Experimental, Mice, Molecular Sequence Data, Proteins, Receptors, Aryl Hydrocarbon, Sequence Alignment, Sequence Analysis, DNA, Tetrachlorodibenzodioxin, Transcription, Genetic, Tumor Cells, Cultured
J. Biol. Chem.
Date: Apr. 04, 1997
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