Ebp1 is a dsRNA-binding protein associated with ribosomes that modulates eIF2α phosphorylation
Ebp1 is a dsRNA-binding protein associated with ribosomes that modulates eIF2α phosphorylation
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DOI：
10.1016/j.bbrc.2006.03.205
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发表时间：
2006-06-09
影响因子：
3.1
通讯作者：
Draetta, GF
中科院分区：
文献类型：
--
作者：
Squatrito, M;Mancino, M;Draetta, GF
dsRNA 结合域 (dsRBD) 是参与不同细胞过程（从 RNA 编辑和加工到翻译控制）的不断扩大的蛋白质家族的特征。在这里，我们提供的证据表明，Ebp1（一种细胞生长调节蛋白，是核糖核蛋白 (RNP) 复合物的一部分）包含 dsRBD，并且该结构域介导其与 dsRNA 的相互作用。 Ebp1 dsRBD 的缺失会损害其核仁定位及其形成 RNP 复合物的能力。我们发现，在细胞质中，Ebp1 与成熟核糖体相关，并且它能够抑制真核起始因子 2 α (eIF2 α) 中丝氨酸 51 的磷酸化。为了响应各种细胞应激，eIF2a 被不同的蛋白激酶（PKR、PERK、GCN2. 和 HRI）磷酸化，该事件导致蛋白质翻译关闭。 HeLa 细胞中 Ebp1 的过度表达能够保护 eIF2 α 在稳定状态下以及对各种治疗的反应中免受磷酸化。我们证明 Ebp1 与 PKR 蛋白激酶相互作用并被 PKR 蛋白激酶磷酸化。我们的结果表明，Ebp1 是一种新的 dsRNA 结合蛋白，可作为 eIF2 α 磷酸化的细胞抑制剂，表明它可能参与蛋白质翻译控制。 (c) 2006 Elsevier Inc. 保留所有权利。
dsRNA-binding domains (dsRBDs) characterize an expanding family of proteins involved in different cellular processes, ranging from RNA editing and processing to translational control. Here we present evidence that Ebp1, a cell growth regulating protein that is part of ribonucleoprotein (RNP) complexes, contains a dsRBD and that this domain mediates its interaction with dsRNA. Deletion of Ebp1's dsRBD impairs its localization to the nucleolus and its ability to form RNP complexes. We show that in the cytoplasm, Ebp1 is associated with mature ribosomes and that it is able to inhibit the phosphorylation of serine 51 in the eukaryotic initiation factor 2 alpha (eIF2 alpha). In response to various cellular stress, eIF2a is phosphorylated by distinct protein kinases (PKR, PERK, GCN2. and HRI), and this event results in protein translation shut-down. Ebp1 overexpression in HeLa cells is able to protect eIF2 alpha from phosphorylation at steady state and also in response to various treatments. We demonstrate that Ebp1 interacts with and is phosphorylated by the PKR protein kinase. Our results demonstrate that Ebp1 is a new dsRNA-binding protein that acts as a cellular inhibitor of eIF2 alpha phosphorylation suggesting that it could be involved in protein translation control. (c) 2006 Elsevier Inc. All rights reserved.