Transcriptional activation function of the mouse Ah receptor nuclear translocator.
We cloned from mouse hepatoma cells a cDNA which encodes the Ah receptor nuclear translocator (Arnt). Sequence comparisons reveal 89% nucleotide and 92% amino acid identity between mouse and human Arnt. Transfection of the cDNA into Arnt-defective mouse hepatoma cells fully restores their responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), indicating that the cDNA encodes a functional Arnt protein. Transfection of the cDNA into wild type mouse hepatoma cells increases the magnitude, but not the sensitivity, of the transcriptional response to TCDD. Analyses of mutants indicate that Arnt has a modular organization. The unit that mediates both heterodimerization with the liganded Ah receptor and DNA recognition is functionally distinct from the unit that mediates transcriptional activation. A 96-amino acid, C-terminal domain of Arnt, which includes a glutamine-rich region, confers transcriptional activation capability upon the protein.
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305-5332.
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Whitlock
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008114:Liver Neoplasms, Experimental; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
C497396:ARNT protein, human; C497397:Arnt protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator