Abstract
The unliganded aryl hydrocarbon receptor (AhR) exists in the cytoplasm in a tetrameric 9S core complex, consisting of the AhR ligand-binding subunit, a dimer of hsp90, and the hepatitis B virus X-associated protein 2 (XAP2), an immunophilin-related protein sharing homologous regions with FKBP12 and FKBP52. Interactions between the recently identified XAP2 subunit and other members of the unliganded AhR complex and its precise role in the AhR signal transduction pathway are presently unknown. Mapping studies indicate that XAP2 requires the PAS, hsp90, and ligand binding domain(s) of the AhR for binding, and that both proteins directly interact in the absence of hsp90. XAP2 is also able to interact with hsp90 complexes in the absence of the AhR, and C-terminal sequences of XAP2 are required for this interaction. XAP2 binds to the C-terminal end of hsp90, which contains a tetratricopeptide repeat domain acceptor site, whereas the AhR binds to a domain in the middle of hsp90. XAP2 was not found to be associated with the AhR-Arnt heterocomplex either in vitro or in nuclear extracts isolated from Hepa 1 cells treated with TCDD. Transient expression of XAP2 in COS-1 cells resulted in enhanced cytosolic AhR levels, suggesting a role for XAP2 in regulating the rate of AhR turnover.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Aryl Hydrocarbon Receptor Nuclear Translocator
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Basic Helix-Loop-Helix Transcription Factors
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COS Cells
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Cell Nucleus / metabolism
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Cell-Free System
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Cytosol / metabolism
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DNA-Binding Proteins*
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HSP90 Heat-Shock Proteins / chemistry*
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HSP90 Heat-Shock Proteins / metabolism
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Helix-Loop-Helix Motifs
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Hepatitis B virus / physiology
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Immunophilins / physiology*
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Intracellular Signaling Peptides and Proteins
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Ligands
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Macromolecular Substances
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Mice
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / physiology
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Protein Binding
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Proteins / chemistry*
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Proteins / metabolism
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Proteins / physiology*
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Receptors, Aryl Hydrocarbon / chemistry*
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Receptors, Aryl Hydrocarbon / metabolism
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Trans-Activators / chemistry
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Tumor Cells, Cultured
Substances
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Arnt protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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HSP90 Heat-Shock Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Macromolecular Substances
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Peptide Fragments
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Proteins
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Receptors, Aryl Hydrocarbon
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Trans-Activators
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Transcription Factors
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aryl hydrocarbon receptor-interacting protein
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Aryl Hydrocarbon Receptor Nuclear Translocator
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endothelial PAS domain-containing protein 1
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Immunophilins