title: Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression.
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.
authors.affiliation: Center for Biotechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Dahlman-Wright
authors.forename: T
authors.initials: T
authors.lastname: Almlöf
authors.forename: I J
authors.initials: IJ
authors.lastname: McEwan
authors.forename: J A
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: A P
authors.initials: AP
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010449:Peptide Mapping; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014170:Transformation, Genetic
chemical_list: D010446:Peptide Fragments; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins