Transcriptional activation function of the mouse Ah receptor nuclear translocator

Abstract

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.