Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein

Shu Takahashi, Hideki Wakui, Jan Åke Gustafsson, Johanna Zilliacus, Hideaki Itoh

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity. MIZ has been approved in Japan and combination therapy with MIZ and glucocorticoids has been used after renal transplantation and for lupus nephritis and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ-binding proteins. 14-3-3 proteins interact with many proteins involved in cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR interaction enhances the transcriptional activity of the receptor. We show that MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of GR and 14-3-3 η dose dependently in vitro. MIZ also has a stimulatory effect on transcriptional activation by the GR. Our results point to the possibility that one mechanism for the therapeutic effect of MIZ could be to regulate the GR function via 14-3-3 proteins. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)87-92
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume274
Issue number1
DOIs
StatePublished - Jul 21 2000

Keywords

  • 14-3-3
  • Glucocorticoid receptor
  • Immunosuppression
  • Mizoribine
  • Nuclear receptor
  • Transactivation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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