Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species
Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species
复制标题
DOI：
10.1128/mcb.26.1.277-292.2006
复制
发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Sorensen, PHB
中科院分区：
文献类型：
--
作者：
Evdokimova, V;Ruzanov, P;Sorensen, PHB
YB-1是一种广泛特异性的RNA结合蛋白，参与mRNA转录、剪接、翻译和稳定性的调节。在胚细胞和体细胞中，YB-1及其相关蛋白是无转录活性的信使核糖核蛋白颗粒（mRNP）的主要成分，并且主要负责mRNA在沉默状态下的储存。然而，调控YB-1的阻遏物活性的机制还不清楚。在这里，我们证明了YB-1与mRNA的加帽5'末端的关联通过丝氨酸/苏氨酸蛋白激酶Akt的磷酸化来调节。与其非磷酸化形式相反，磷酸化YB-1不能抑制帽依赖性，但不是内部核糖体进入位点依赖性的报告mRNA在体外翻译。我们还表明，类似于YB-1，Akt与失活的mRNP和激活的Akt可以减轻YB-1结合的mRNA的翻译抑制。使用Affyssin微阵列，我们发现许多YB-1相关的信息编码应激和生长相关蛋白，提出了一种有趣的可能性，即Akt介导的YB-1磷酸化可以部分增加调节细胞增殖，致癌转化和应激反应的蛋白质的产生。
YB-1 is a broad-specificity RNA-binding protein that is involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal and somatic cells, YB-1 and related proteins are major components of translationally inactive messenger ribonucleoprotein particles (mRNPs) and are mainly responsible for storage of mRNAs in a silent state. However, mechanisms regulating the repressor activity of YB-1 are not well understood. Here we demonstrate that association of YB-1 with the capped 5' terminus of the mRNA is regulated via phosphorylation by the serine/threonine protein kinase Akt. In contrast to its nonphosphorylated form, phosphorylated YB-1 fails to inhibit cap-dependent but not internal ribosome entry site-dependent translation of a reporter mRNA in vitro. We also show that similar to YB-1, Akt is associated with inactive mRNPs and that activated Akt may relieve translational repression of the YB-1-bound mRNAs. Using Affymetrix microarrays, we found that many of the YB-1-associated messages encode stress- and growth-related proteins, raising the intriguing possibility that Akt-mediated YB-1 phosphorylation could, in part, increase production of proteins regulating cell proliferation, oncogenic transformation, and stress response.