Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression

Karin Dahlman-Wright, Tova Almlöf, Iain J. Mcewan, Jan Åke Gustafsson, Anthony P.H. Wright

    Research output: Contribution to journalArticlepeer-review

    89 Scopus citations

    Abstract

    Previous deletion analysis localized the major transactivation function of the human glucocorticoid receptor to a 185-amino acid segment close to the N terminus of the receptor protein. This region was named τ1 [Hollenberg, S. M. and Evans, R. M. (1989) Cell 55, 899-906]. To delineate the smallest active region within τ1, we have systematically tested the transactivation capacity of deletion derivatives of the τ1 domain, fused to the glucocorticoid receptor DNA-binding domain, in yeast cells. Internal scanning deletions suggested that residues near the C terminus of τ1 are most important for activity. Deletions of N-terminal and C-terminal sequences identified a 41-amino acid 'core' region near the C terminus of τ1 that is crucial for τ1 function. Small peptide fragments containing the τ1 core region are competent for transactivation, while regions outside the τ1 core are not active. We have previously demonstrated that the intact τ1 domain squelches the activity of a minimal promoter in vivo and in vitro, suggesting involvement of interactions with a component/components of the basal transcription machinery in the mechanism of transactivation. This activity was maintained in the τ1 core-containing segments.

    Original languageEnglish (US)
    Pages (from-to)1619-1623
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume91
    Issue number5
    DOIs
    StatePublished - Mar 1 1994

    ASJC Scopus subject areas

    • General

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