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Research Article

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

K Dahlman-Wright, T Almlöf, I J McEwan, J A Gustafsson, and A P Wright
PNAS March 1, 1994 91 (5) 1619-1623; https://doi.org/10.1073/pnas.91.5.1619
K Dahlman-Wright
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
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T Almlöf
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
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I J McEwan
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
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J A Gustafsson
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
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A P Wright
Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
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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 tau 1 [Hollenberg, S. M. & Evans, R. M. (1988) Cell 55, 899-906]. To delineate the smallest active region within tau 1, we have systematically tested the transactivation capacity of deletion derivatives of the tau 1 domain, fused to the glucocorticoid receptor DNA-binding domain, in yeast cells. Internal scanning deletions suggested that residues near the C terminus of tau 1 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 tau 1 that is crucial for tau 1 function. Small peptide fragments containing the tau 1 core region are competent for transactivation, while regions outside the tau 1 core are not active. We have previously demonstrated that the intact tau 1 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 tau 1 core-containing segments.

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Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression.
K Dahlman-Wright, T Almlöf, I J McEwan, J A Gustafsson, A P Wright
Proceedings of the National Academy of Sciences Mar 1994, 91 (5) 1619-1623; DOI: 10.1073/pnas.91.5.1619

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Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression.
K Dahlman-Wright, T Almlöf, I J McEwan, J A Gustafsson, A P Wright
Proceedings of the National Academy of Sciences Mar 1994, 91 (5) 1619-1623; DOI: 10.1073/pnas.91.5.1619
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