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

• DOI: 10.1038/sj.emboj.7600477
• Publication Date: 2004-11-11T10:08:56Z
• Authors: Martin Schmidlin; Min Lu; Sabrina A Leuenbe...; Georg Stoecklin; Michel Mallaun; Brigitte Gross; Roberto Gherzi; Daniel Hess; Brian A Hemmings; Christoph Moroni
• Keywords: TATA-Binding Protein Associated Factors; 0303 health sciences; RNA Stability; Protein Serine-Threonine Kinases; Recombinant Proteins; Mice; 03 medical and health sciences; 14-3-3 Proteins; Genes, Reporter; Proto-Oncogene Proteins; NIH 3T3 Cells; Serine; Animals; Insulin; RNA, Messenger; Phosphorylation; Proto-Oncogene Proteins c-akt; Protein Binding

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.