Transcriptional activation domains of the Ah receptor and Ah receptor nuclear translocator

Kazuhiro Sogawa, Koichi Iwabuchi, Hisaku Abe, Yoshiaki Fujii-Kuriyama

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    53 Citations (Scopus)

    Abstract

    The Ah receptor (AhR) and Ah receptor nuclear translocator (Arnt) heterodimer bind the xenobiotic-responsive element (XRE) sequence in the upstream, region of the genes for some drug-metabolizing enzymes, such as P4501A1 and glutathione S-transferase Ya, to activate their transcription. This paper describes transcriptional activation domains of the AhR and Arnt as examined in vivo by DNA transfection experiments using GAL4-AhR or GAL4-Arnt chimeric plasmids and a reporter plasmid containing five GAL4 DNA binding sites. The major activation domain of Arnt was localized in a short segment of the C-terminal 34 amino acids, while the glutamine-rich domain of Arnt showed no transcriptional activity. This activation domain of Arnt could be further divided into two subdomains with some sequence similarity. Point mutation analysis of one of the subdomains revealed that bulky hydrophobic amino acids and neighboring acidic amino acids were necessary for the transcription-enhancing activity of Arnt. The C-terminal half of the AhR showed a strong transcription-stimulating activity, apparently five times as strong as that of Arnt. Further analysis of the activity revealed that the C-terminal transcriptional activity was distributed in several activation domains, one of which is rich in glutamine residues. These results indicate that the glutamine-rich domains of the AhR and Arnt function differently in the heterodimer regulatory complex. Previously, we showed that the enhancer activity of XRE was repressed by E1A proteins, especially the 12S form of E1A. Cotransfection experiments using an E1A12S expression plasmid and a GAL4-AhR or GAL4-Arnt expression plasmid demonstrated that E1A protein rather predominantly inhibited the transcriptional activity of Arnt.

    Original languageEnglish
    Pages (from-to)612-620
    Number of pages9
    JournalJournal of Cancer Research and Clinical Oncology
    Volume121
    Issue number9-10
    DOIs
    Publication statusPublished - 1995 Sep 1

    Keywords

    • PAS protein
    • Transactivation
    • Xenobiotic induction

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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