Translation Initiation Requires Cell Division Cycle 123 (Cdc123) to Facilitate Biogenesis of the Eukaryotic Initiation Factor 2 (eIF2)
Translation Initiation Requires Cell Division Cycle 123 (Cdc123) to Facilitate Biogenesis of the Eukaryotic Initiation Factor 2 (eIF2)
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翻译起始需要细胞分裂周期 123 (Cdc123) 来促进真核起始因子 2 (eIF2) 的生物合成
DOI：
10.1074/jbc.m113.472290
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
W. Seufert
中科院分区：
文献类型：
--
作者：
Angelika F Perzlmaier;F. Richter;W. Seufert
背景：真核生物翻译起始因子2（eIF 2）是一种异源三聚体G蛋白。结果：Cdc 123是一种保守的细胞增殖蛋白，它与eIF 2 γ亚基结合，促进eIF 2复合物的形成。结论：Cdc 123是一种特异性的eIF 2组装因子，在蛋白质合成过程中起重要作用。意义：本研究描述了真核生物翻译起始途径中的一个新步骤。真核生物翻译起始因子2（eIF 2）是蛋白质合成的起始及其对生理需求的调节的核心。eIF 2是一种异源三聚体G蛋白，通过鸟嘌呤核苷酸交换激活，将引发剂甲硫氨酰-tRNA递送至核糖体。在这里，我们报告的eIF 2复合物在体内的组装依赖于Cdc 123，真核生物中保守的细胞增殖蛋白。芽殖酵母中的CDC 123突变减少了eIF 2亚基的结合，减少了多核糖体水平，并增加了GCN 4表达，表明Cdc 123对eIF 2活性至关重要。Cdc 123结合未组装的eIF 2 γ亚基，但不结合eIF 2复合物，并且eIF 2 γ的C-末端结构域III区域对于Cdc 123结合是必要的和充分的。结合位点的改变揭示了Cdc 123结合、eIF 2 γ的生物学功能及其与eIF 2 α和eIF 2 β组装的能力之间的严格相关性。有趣的是，高水平的Cdc 123中和了组装缺陷，恢复了eIF 2 γ突变体的生物学功能。此外，eIF 2亚基的组合过表达拯救了一个原本不可活的cdc 123缺失突变体。因此，Cdc 123是一个特定的eIF 2组装因子的蛋白质合成的开始是必不可少的。人类Cdc 123由疾病风险位点编码，因此，Cdc 123对eIF 2生物合成的控制可能与正常细胞生理学和人类健康相关。这项工作确定了真核翻译起始途径中的一个新步骤，并将生物化学功能分配给对真核细胞生长和活力至关重要的蛋白质。
Background: The eukaryotic translation initiation factor 2 (eIF2) is a heterotrimeric G-protein. Results: Cdc123, a conserved cell proliferation protein, binds the unassembled eIF2γ subunit to promote eIF2 complex formation. Conclusion: Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Significance: This study describes a novel step in the eukaryotic translation initiation pathway. The eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and its modulation in response to physiological demands. eIF2, a heterotrimeric G-protein, is activated by guanine nucleotide exchange to deliver the initiator methionyl-tRNA to the ribosome. Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell proliferation protein conserved among eukaryotes. Mutations of CDC123 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased GCN4 expression indicating that Cdc123 is critical for eIF2 activity. Cdc123 bound the unassembled eIF2γ subunit, but not the eIF2 complex, and the C-terminal domain III region of eIF2γ was both necessary and sufficient for Cdc123 binding. Alterations of the binding site revealed a strict correlation between Cdc123 binding, the biological function of eIF2γ, and its ability to assemble with eIF2α and eIF2β. Interestingly, high levels of Cdc123 neutralized the assembly defect and restored the biological function of an eIF2γ mutant. Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 deletion mutant. Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Human Cdc123 is encoded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for normal cell physiology and human health. This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells.
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DOI：
10.1073/pnas.86.8.2784
发表时间：
1989-04-01
影响因子：
11.1
作者：
CIGAN, AM;PABICH, EK;DONAHUE, TF
通讯作者：
DONAHUE, TF
影响因子：
7.2
作者：
Hinnebusch, Alan G.;Lorsch, Jon R.
通讯作者：
Lorsch, Jon R.
影响因子：
16
作者：
Borck, Guntram;Shin, Byung-Sik;Stiller, Barbara;Mimouni-Bloch, Aviva;Thiele, Holger;Kim, Joo-Ran;Thakur, Meghna;Skinner, Cindy;Aschenbach, Lara;Smirin-Yosef, Pola;Har-Zahav, Adi;Nuernberg, Gudrun;Altmueller, Janine;Frommolt, Peter;Hofmann, Kay;Konen, Osnat;Nuernberg, Peter;Munnich, Arnold;Schwartz, Charles E.;Gothelf, Doron;Colleaux, Laurence;Dever, Thomas E.;Kubisch, Christian;Basel-Vanagaite, Lina
通讯作者：
Basel-Vanagaite, Lina
影响因子：
16
作者：
Kim W;Bennett EJ;Huttlin EL;Guo A;Li J;Possemato A;Sowa ME;Rad R;Rush J;Comb MJ;Harper JW;Gygi SP
通讯作者：
Gygi SP