Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127
Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127
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DOI：
10.1016/j.bbamcr.2015.04.004
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发表时间：
2015-07-01
影响因子：
5.1
通讯作者：
Donella-Deana, Arianna
中科院分区：
文献类型：
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作者：
Borgo, Christian;Franchin, Cinzia;Donella-Deana, Arianna
在真核生物蛋白质合成中，翻译起始因子3（eIF 3）是翻译起始机制的募集和组装中的关键参与者。哺乳动物eIF 3由13个亚基组成，包括在eIF 3复合物形成和与40 S核糖体亚基相互作用中起稳定作用的松散缔合的eIF 3 j亚基。通过免疫共沉淀和质谱分析，我们证明了蛋白激酶CK 2与eIF 3 j在Ser 127处相互作用并使其磷酸化。CX-4945对CK 2活性的抑制或siRNA对CK 2催化亚基表达的下调导致j-亚基从eIF 3复合物中解离，如甘油梯度沉降所判断的。这一发现证明了eIF 3 j的CK 2磷酸化是其与eIF 3复合物结合的先决条件。Ser 127 Ala-eIF 3 j突变体的表达损害了突变的j亚基与其他eIF 3亚基的相互作用以及整体蛋白质合成。综上所述，我们的数据表明，CK 2-磷酸化的eIF 3 j在Ser 127促进组装的eIF 3复合物，翻译起始机制的激活中的一个关键步骤。(C)2015爱思唯尔B. V.保留所有权利。
In eukaryotic protein synthesis the translation initiation factor 3 (eIF3) is a key player in the recruitment and assembly of the translation initiation machinery. Mammalian eIF3 consists of 13 subunits, including the loosely associated eIF3j subunit that plays a stabilizing role in the eIF3 complex formation and interaction with the 40S ribosomal subunit. By means of both co-immunoprecipitation and mass spectrometry analyses we demonstrate that the protein kinase CK2 interacts with and phosphorylates eIF3j at Ser127. Inhibition of CK2 activity by CX-4945 or down-regulation of the expression of CK2 catalytic subunit by siRNA cause the dissociation of j-subunit from the eIF3 complex as judged from glycerol gradient sedimentation. This finding proves that CK2-phosphorylation of eIF3j is a prerequisite for its association with the eIF3 complex. Expression of Ser127Ala-eIF3j mutant impairs both the interaction of mutated j-subunit with the other eIF3 subunits and the overall protein synthesis. Taken together our data demonstrate that CK2-phosphorylation of eIF3j at Ser127 promotes the assembly of the eIF3 complex, a crucial step in the activation of the translation initiation machinery. (C) 2015 Elsevier B.V. All rights reserved.