Article
- The EMBO Journal (2004) 23, 4760 - 4769
- doi:10.1038/sj.emboj.7600477
Published online: 11 November 2004
Subject Categories:
The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B
Martin Schmidlin1, Min Lu1, Sabrina A Leuenberger1, Georg Stoecklin2, Michel Mallaun1, Brigitte Gross1, Roberto Gherzi3, Daniel Hess4, Brian A Hemmings4 and Christoph Moroni1
- Institute for Medical Microbiology, University of Basel, Basel, Switzerland
- Division of Rheumatology and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Gene Transfer Laboratory, Instituto Nazionale per la Ricerca sul Cancro, Genova, Italy
- Friedrich Miescher Institute, Basel, Switzerland
Correspondence to:
Christoph Moroni, Institute für Medizinische Mikrobiologie, Universität Basel, Petersplatz 10, Basel 4003, Switzerland. Tel.: +41 61 267 3264; Fax: +41 61 267 3283; E-mail: christoph.moroni@unibas.ch
Received 22 July 2004; Accepted 15 October 2004
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.
Keywords:
- exosome,
- insulin,
- mRNA turnover,
- PKB,
- zinc-finger protein
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