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 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.
Schmidlin
Martin
M
Institute for Medical Microbiology, University of Basel, Basel, Switzerland.
Lu
Min
M
Leuenberger
Sabrina A
SA
Stoecklin
Georg
G
Mallaun
Michel
M
Gross
Brigitte
B
Gherzi
Roberto
R
Hess
Daniel
D
Hemmings
Brian A
BA
Moroni
Christoph
C
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D017930:Genes, Reporter; D007328:Insulin / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*
D048948:14-3-3 Proteins; C441028:BRF1 protein, human; D007328:Insulin; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D035381:TATA-Binding Protein Associated Factors; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt