RU486-induced Glucocorticoid Receptor Agonism Is Controlled by the Receptor N Terminus and by Corepressor Binding*

Glucocorticoid-induced gene transcription has been shown to be mediated by coactivators bound to the glucocorticoid receptor (GR). The glucocorticoid antagonist RU486 interferes with the steroid-mediated activation and can also exhibit partial agonist activity, a response in which corepressors have been implicated. Here we have shown that deletion of the N terminus of GR totally abolishes the agonist activity of RU486. Furthermore, we have demonstrated that corepressors bind directly to the RU486-bound GR as determined by glutathione S-transferase pull-down, mammalian two-hybrid assay, and coimmunoprecipitation. Fine mapping of the interaction regions within GR and the corepressor NCoR reveals a complex interaction profile that involves a number of domains in each protein. Notably, the N and the C termini of GR are both involved in corepressor binding. Thus, the N terminus of GR is a major determinant for RU486-dependent NCoR interaction as well as for RU486-mediated agonist activity.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-07-19

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M203268200PMID 12011091
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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