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https://hdl.handle.net/2440/28079
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Type: | Journal article |
Title: | Definition of a dioxin receptor mutant that is a constitutive activator of transcription - Delineation of overlapping repression and ligand binding functions within the PAS domain |
Author: | McGuire, J. Okamoto, K. Whitelaw, M. Tanaka, H. Poellinger, L. |
Citation: | Journal of Biological Chemistry, 2001; 276(45):41841-41849 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2001 |
ISSN: | 0021-9258 1083-351X |
Organisation: | Centre for the Molecular Genetics of Development |
Statement of Responsibility: | Jacqueline McGuire, Kensaku Okamoto, Murray L. Whitelaw, Hirotoshi Tanaka, and Lorenz Poellinger |
Abstract: | The intracellular dioxin (aryl hydrocarbon) receptor is a ligand-activated transcription factor that mediates the adaptive and toxic responses to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and structurally related congeners. Whereas the ligand-free receptor is characterized by its association with the molecular chaperone hsp90, exposure to ligand initiates a multistep activation process involving nuclear translocation, dissociation from the hsp90 complex, and dimerization with its partner protein Arnt. In this study, we have characterized a dioxin receptor deletion mutant lacking the minimal ligand-binding domain of the receptor. This mutant did not bind ligand and localized constitutively to the nucleus. However, this protein was functionally inert since it failed to dimerize with Arnt and to bind DNA. In contrast, a dioxin receptor deletion mutant lacking the minimal PAS B motif but maintaining the N-terminal half of the ligand-binding domain showed constitutive dimerization with Arnt, bound DNA, and activated transcription in a ligand-independent manner. Interestingly, this mutant showed a more potent functional activity than the dioxin-activated wild-type receptor in several different cell lines. In conclusion, the constitutively active dioxin receptor may provide an important mechanistic tool to investigate receptor-mediated regulatory pathways in closer detail. |
Keywords: | CHO Cells Animals DNA-Binding Proteins Trans-Activators Receptors, Aryl Hydrocarbon Transcription Factors Ligands Binding Sites Response Elements Dimerization Mutation Cricetinae Aryl Hydrocarbon Receptor Nuclear Translocator |
Description: | Copyright © 2001 by The American Society for Biochemistry and Molecular Biology |
DOI: | 10.1074/jbc.M105607200 |
Published version: | http://www.jbc.org/cgi/content/abstract/276/45/41841 |
Appears in Collections: | Aurora harvest 2 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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