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 journalArticle

77 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

Fingerprint Dive into the research topics of 'Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression'. Together they form a unique fingerprint.

Cite this