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

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 stab...

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Bibliographic Details
Published in:The EMBO journal 2004-12, Vol.23 (24), p.4760-4769
Main Authors: Schmidlin, Martin, Lu, Min, Leuenberger, Sabrina A, Stoecklin, Georg, Mallaun, Michel, Gross, Brigitte, Gherzi, Roberto, Hess, Daniel, Hemmings, Brian A, Moroni, Christoph
Format: Article
Language:English
Subjects:
14-3-3 Proteins - metabolism
Animals
exosome
Genes, Reporter
insulin
Insulin - metabolism
Mice
mRNA turnover
NIH 3T3 Cells
Phosphorylation
PKB
Protein Binding
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
RNA Stability
RNA, Messenger - metabolism
Serine - metabolism
TATA-Binding Protein Associated Factors - genetics
TATA-Binding Protein Associated Factors - metabolism
zinc‐finger protein
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7600477