Role of hydrophobic amino acid clusters in the transactivation activity of the human glucocorticoid receptor

Tova Almlöf, Jan Åke Gustafsson, Anthony P.H. Wright

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62 Scopus citations


We have performed a mutagenesis analysis of the 58-amino-acid τ1-core peptide, which represents the core transactivation activity of the τ1 transactivation domain from the glucocorticoid receptor. Mutants with altered activity were identified by phenotypic screening in the yeast Saccharomyces cerevisiae. Most mutants with reduced activity had substitutions of hydrophobic amino acids. Most single-substitution mutants with reduced activity were localized near the N terminus of the τ1-core within a segment that has been shown previously to have a propensity for α-helix conformation, suggesting that this helical region is of predominant importance. The particular importance of hydrophobic residues within this region was confirmed by comparing the activities of alanine substitutions of the hydrophobic residues in this and two other helical regions. The hydrophobic residues were shown to be important for the transactivation activity of both the isolated τ1-core and the intact glucocorticoid receptor in mammalian cells. Rare mutations in helical regions I and II gave rise to increased transcriptional activation activity. These mutations increase the hydrophobicity of hydrophobic patches on each of these helices, suggesting a relationship between the hydrophobicity of the patches and transactivation activity. However, certain nonhydrophobic residues are also important for activity. Interestingly, helical region I partially matches a consensus motif found in the retinoic acid receptor, VP16, and several other activator proteins.

Original languageEnglish (US)
Pages (from-to)934-945
Number of pages12
JournalMolecular and Cellular Biology
Issue number2
StatePublished - Feb 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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