Journal of Biological Chemistry
Volume 273, Issue 5, 30 January 1998, Pages 2895-2904
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CELL BIOLOGY AND METABOLISM
Nuclear Localization and Export Signals of the Human Aryl Hydrocarbon Receptor*

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The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that binds DNA in the form of a heterodimer with the Ahr nuclear translocator (hypoxia-inducible factor 1β). We found in this study that Ahr contains both nuclear localization and export signals in the NH2-terminal region. A fusion protein composed of β-galactosidase and full-length Ahr translocates from the cytoplasm to the nucleus in a ligand-dependent manner. However, a fusion protein lacking the PAS (Per-Ahr nuclear translocator-Sim homology) domain of the Ahr showed strong nuclear localization activity irrespective of the presence or absence of ligand. A minimum bipartite Ahr nuclear localization signal (NLS) consisting of amino acid residues 13–39 was identified by microinjection of fused proteins with glutathioneS-transferase-green fluorescent protein. A NLS having mutations in bipartite basic amino acids lost nuclear translocation activity completely, which may explain the reduced binding activity to the NLS receptor, PTAC58. A 21-amino acid peptide (residues 55–75) containing the Ahr nuclear export signal is sufficient to direct nuclear export of a microinjected complex of glutathioneS-transferase-Ahr-green fluorescent protein. These findings strongly suggest that Ahr act as a ligand- and signal-dependent nucleocytoplasmic shuttling protein.

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*

This work was supported in part by a grant for advanced research on cancer from the Ministry of Education, Science, Sports, and Culture of Japan and a research grant from the Ministry of Health and Welfare of Japan for the Second Term Comprehensive 10-Year Strategy for Cancer Control.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.