The nuclear-receptor interacting protein (RIP) 140 binds to the human glucocorticoid receptor and modulates hormone-dependent transactivation

S H Windahl, E Treuter, J Ford, J Zilliacus, J A Gustafsson, I J McEwan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The glucocorticoid receptor (CR) regulates target gene expression in response to corticosteroid hormones. We have investigated the mechanism of transcriptional activation by the GR by studying the role of the receptor interacting protein RIP140. Both in vivo and in vitro protein-protein interaction assays revealed a ligand-dependent interaction between the GR and RIP140. The ligand binding domain of the GR was sufficient for this interaction, while both the N- and C-terminal regions of RIP140 bound to the receptor. In a yeast transactivation assay RIP140 and SRC-1, a member of the steroid receptor coactivator family of proteins, both enhanced the transactivation activity of a GR protein (GR Delta(tau 1)) in which the potent N-terminal tau(1) transactivation domain has been deleted. In contrast, in COS-7 cells increasing amounts of RIP140 significantly inhibited GR Delta(tau 1) function. In cotransfection studies in COS-7 cells, RIP140 also inhibited receptor activity in presence of both SRC-1 and the coactivator protein CBP together. Thus, in yeast cells a stimulation of receptor activity was observed, while in mammalian cells RIP140 repressed GR function. Taken together, these data suggest that, (1) RIP140 is a target protein for the CR and (2) RIP140 can modulate the transactivation activity of the receptor. (C) 2000 Elsevier Science Ltd. Ail rights reserved.

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Volume71
Issue number3-4
DOIs
Publication statusPublished - 15 Dec 1999

Keywords

  • transcriptional activation
  • histone acetyltransferase
  • gene activation
  • estrogen-receptor
  • steroid-receptors
  • conserved region
  • response element
  • TFIID complex
  • in-vitro
  • domain

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