Akt phosphorylation of La regulates specific mRNA translation in glial progenitors
Akt phosphorylation of La regulates specific mRNA translation in glial progenitors
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DOI：
10.1038/onc.2008.376
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发表时间：
2009-01-08
期刊：
影响因子：
8
通讯作者：
Holland, E. C.
中科院分区：
文献类型：
--
作者：
Brenet, F.;Socci, N. D.;Holland, E. C.
Akt信号通路活性随着正常组织向恶性转化而增加，并通过多种机制调节特定信使RNA（mRNA）的翻译。我们已经确定了一个这样的机制Akt依赖的翻译控制涉及狼疮自身抗原La。La是一种RNA相关蛋白，含有多个运输元件，以支持与不同亚细胞位置的RNA相互作用。我们在这里表明，La蛋白是丝氨酸/苏氨酸蛋白激酶Akt对苏氨酸301的直接靶点，并且La在小鼠神经胶质祖细胞中的核出口，以及其与多核糖体的关联由Akt活性调节。使用功能的方法，以确定网络的基因受La在细胞质中的多核糖体结合的mRNA的微阵列分析，我们发现，La结合34%的多核糖体结合的mRNA和调节下KRas/Akt激活的特定池的mRNA的表达。因此，La似乎是Akt介导的这些转录本在鼠神经胶质细胞中的翻译调节的重要贡献者。
The Akt signaling pathway activity increases as normal tissue progresses to malignant transformation, and regulates the translation of specific messenger RNAs (mRNAs) through multiple mechanisms. We have identified one such mechanism of Akt-dependent translation control as involving the lupus autoantigen La. La is an RNA-associated protein that contains multiple trafficking elements to support the interaction with RNAs in different subcellular locations. We show here that the La protein is a direct target of the serine/threonine protein kinase Akt on threonine 301, and La nuclear export in mouse glial progenitors, as well as its association with polysomes is modulated by Akt activity. Using a functional approach to determine the network of genes affected by La in the cytoplasm by microarray analysis of polysome-bound mRNAs, we found that La binds 34% of the polysome bound mRNAs and regulates the expression of a specific pool of mRNAs under KRas/Akt activation. Therefore, La appears to be an important contributor to Akt-mediated translational regulation of these transcripts in murine glial cells.