Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism.
Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism.
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DOI：
10.1016/j.celrep.2021.109376
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发表时间：
2021-07-13
期刊：
影响因子：
8.8
通讯作者：
Asano K
中科院分区：
文献类型：
--
作者：
Singh CR;Glineburg MR;Moore C;Tani N;Jaiswal R;Zou Y;Aube E;Gillaspie S;Thornton M;Cecil A;Hilgers M;Takasu A;Asano I;Asano M;Escalante CR;Nakamura A;Todd PK;Asano K
eIF 5-mimic protein（5 MP）是一种翻译调节蛋白，其结合核糖体小亚基并调节其活性。5 MP被提议用于重新编程癌症中癌基因的非AUG翻译速率，但其在控制非AUG启动的有害重复肽产物合成中的作用，例如在脆性X相关震颤共济失调综合征（FXTAS）中观察到的FMRpolyG，尚不清楚。在这里，我们表明5 MP可以通过一种常见机制以取决于其与eIF 3相互作用的方式抑制一般和重复相关的非AUG（RAN）翻译。基本上，5 MP通过PIC内的eIF 3c亚基置换eIF 5，从而提高起始的准确性。在果蝇中，5 MP/Kra在FXTAS疾病模型中抑制神经元毒性并延长寿命。这些结果暗示5 MP在神经变性中保护细胞免受非AUG翻译的不需要的副产物的影响。
eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in Fragile-X associated tremor ataxia syndrome (FXTAS), is unknown. Here we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the PIC, thereby increasing the accuracy of initiation. In Drosophila, 5MP/Kra represses neuronal toxicity and enhances lifespan in a FXTAS disease model. These results implicate 5MP in protecting cells from unwanted byproducts of non-AUG translation in neurodegeneration.
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EIF5或其蛋白质模拟5MP的过表达EIF2函数，并通过延迟重新定位诱导ATF4翻译。
影响因子：
14.9
作者：
Kozel C;Thompson B;Hustak S;Moore C;Nakashima A;Singh CR;Reid M;Cox C;Papadopoulos E;Luna RE;Anderson A;Tagami H;Hiraishi H;Slone EA;Yoshino KI;Asano M;Gillaspie S;Nietfeld J;Perchellet JP;Rothenburg S;Masai H;Wagner G;Beeser A;Kikkawa U;Fleming SD;Asano K
通讯作者：
Asano K
影响因子：
3.7
作者：
Hoem, Gry;Larsen, Kenneth Bowitz;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
16.2
作者：
Ash PE;Bieniek KF;Gendron TF;Caulfield T;Lin WL;Dejesus-Hernandez M;van Blitterswijk MM;Jansen-West K;Paul JW 3rd;Rademakers R;Boylan KB;Dickson DW;Petrucelli L
通讯作者：
Petrucelli L
DOI：
10.4161/trla.28387
发表时间：
2014
期刊：
Translation (Austin, Tex.)
影响因子：
--
作者：
Asano K
通讯作者：
Asano K
影响因子：
7
作者：
Ishihama, Y;Oda, Y;Mann, M
通讯作者：
Mann, M