Structure and function of the glucocorticoid receptor

Anthony P.H. Wright, Johanna Zilliacus, Iain J. McEwan, Karin Dahlman-Wright, Tova Almlöf, Jan Carlstedt-Duke, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Glucocorticoids cause changes in the expression of target genes via interaction with an intracellular receptor protein. the glucocorticoid receptor. This signal transduction process can be divided into a number of steps, each of which represents a functional facet of the receptor protein. These steps include (i) receptor transformation to an active form resulting from specific interaction with glucocorticoid steroid hormones, (ii) homo-dimerization, (iii) DNA-binding to specific hormone response elements in the genome and (iv) modulation of the expression levels of linked genes. These aspects of glucocorticoid receptor function have been studied using a combination of tertiary structure determination, biochemical assays and a genetic approach using a yeast system to screen for mutant receptors that are altered in function. The results show that contacts involving both the DNA and steroid binding domains are involved in dimerization and high affinity DNA binding. Genetic experiments have illuminated the role of amino acids within the recognition helix of the DNA-binding domain in discriminating between cognate DNA response elements for the glucocorticoid receptor and closely related binding sites for other nuclear receptors. Squelching experiments suggest that the N-terminal transactivation domain of the receptor contacts components of the general transcriptional machinery that appear to be distinct from the TATA binding protein, TFIID, during transactivation of gene expression by the DNA-bound receptor.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume47
Issue number1-6
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Structure and function of the glucocorticoid receptor'. Together they form a unique fingerprint.

Cite this