The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B

Martin Schmidlin, Min Lu, Sabrina A. Leuenberger, Georg Stoecklin, Michel Mallaun, Brigitte Gross, Roberto Gherzi, Daniel Hess, Brian A. Hemmings, Christoph Moroni

Research output: Contribution to journalArticle

Abstract

Butyrate response factor (BRF1) belongs to the Tis11 family of CCCH zinc-finger proteins, which bind to mRNAs containing an AU-rich element (ARE) in their 3′ untranslated region and promote their deadenylation and rapid degradation. Independent signal transduction pathways have been reported to stabilize ARE-containing transcripts by a process thought to involve phosphorylation of ARE-binding proteins. Here we report that protein kinase B (PKB/Akt) stabilizes ARE transcripts by phosphorylating BRF1 at serine 92 (S92). Recombinant BRF1 promoted in vitro decay of ARE-containing mRNA (ARE-mRNA), yet phosphorylation by PKB impaired this activity. S92 phosphorylation of BRF1 did not impair ARE binding, but induced complex formation with the scaffold protein 14-3-3. In vivo and in vitro data support a model where PKB causes ARE-mRNA stabilization by inactivating BRF1 through binding to 14-3-3.

Original languageEnglish
Pages (from-to)4760-4769
Number of pages10
JournalEMBO Journal
Volume23
Issue number24
DOIs
Publication statusPublished - Dec 8 2004

Keywords

  • Exosome
  • Insulin
  • mRNA turnover
  • PKB
  • Zinc-finger protein

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Schmidlin, M., Lu, M., Leuenberger, S. A., Stoecklin, G., Mallaun, M., Gross, B., Gherzi, R., Hess, D., Hemmings, B. A., & Moroni, C. (2004). The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B. EMBO Journal, 23(24), 4760-4769. https://doi.org/10.1038/sj.emboj.7600477