The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B
The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B
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DOI：
10.1038/sj.emboj.7600477
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发表时间：
2004-12-08
期刊：
影响因子：
11.4
通讯作者：
Moroni, C
中科院分区：
文献类型：
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作者：
Schmidlin, M;Lu, M;Moroni, C
丁酸反应因子（BRF 1）属于CCCH锌指蛋白的Tis 11家族，其与在其30非翻译区中含有富含AU元件（ARE）的mRNA结合并促进其去腺苷化和快速降解。据报道，独立的信号转导途径通过被认为涉及ARE结合蛋白磷酸化的过程来稳定含ARE的转录物。在这里，我们报告蛋白激酶B（PKB/Akt）通过磷酸化BRF 1的丝氨酸92（S92）稳定ARE转录本。重组BRF 1促进体外衰减的ARE-含有mRNA（ARE-mRNA），但磷酸化的PKB损害这种活性。BRF 1的S92磷酸化不损害ARE结合，但诱导与支架蛋白14-3-3形成复合物。体内和体外数据支持PKB通过与14-3-3结合使BRF 1失活而导致ARE-mRNA稳定的模型。
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 30 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.