Schmidlin Martin, Lu Min, Leuenberger Sabrina A, Stoecklin Georg, Mallaun Michel, Gross Brigitte, Gherzi Roberto, Hess Daniel, Hemmings Brian A, Moroni Christoph
Institute for Medical Microbiology, University of Basel, Basel, Switzerland.
EMBO J. 2004 Dec 8;23(24):4760-9. doi: 10.1038/sj.emboj.7600477. Epub 2004 Nov 11.
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.
丁酸反应因子（BRF1）属于CCCH锌指蛋白的Tis11家族，该家族蛋白可与在3'非翻译区含有富含AU元件（ARE）的mRNA结合，并促进其去腺苷酸化和快速降解。据报道，独立的信号转导途径可通过一种被认为涉及ARE结合蛋白磷酸化的过程来稳定含ARE的转录本。在此，我们报告蛋白激酶B（PKB/Akt）通过在丝氨酸92（S92）位点磷酸化BRF1来稳定ARE转录本。重组BRF1促进了含ARE的mRNA（ARE-mRNA）的体外降解，但PKB介导的磷酸化损害了该活性。BRF1的S92磷酸化并不损害ARE结合，但诱导了与支架蛋白14-3-3的复合物形成。体内和体外数据支持这样一种模型，即PKB通过与14-3-3结合使BRF1失活，从而导致ARE-mRNA稳定。
