A novel inhibitor of cap-dependent translation initiation in yeast: P20 competes with eIF4G for binding to eIF4E
A novel inhibitor of cap-dependent translation initiation in yeast: P20 competes with eIF4G for binding to eIF4E
复制标题
DOI：
10.1093/emboj/16.5.1114
复制
发表时间：
1997-03-03
期刊：
影响因子：
11.4
通讯作者：
Trachsel, H
中科院分区：
文献类型：
--
作者：
Altmann, M;Schmitz, N;Trachsel, H
在酿酒酵母中，发现一种名为p20的小蛋白与翻译起始因子eIF 4 E（mRNA帽结合蛋白）相关。我们在这里证明，p20是帽依赖性翻译起始的阻遏物，p20显示氨基酸序列同源性的区域eIF 4G，大亚基的帽结合蛋白复合物eIF 4F，携带的结合位点eIF 4 E。eIF 4G和p20都与eIF 4 E结合，并相互竞争与eIF 4 E的结合。eIF 4 E-p20复合物可结合帽结构并抑制帽依赖性而非帽非依赖性翻译起始：在其5'非翻译区中具有烟草花叶病毒的67个核苷酸Ω序列的mRNA的翻译（其先前显示使翻译帽非依赖性）不受p20抑制。而缺乏Omega序列的相同mRNA的翻译被p20强烈抑制。破坏编码p20的基因CAF 20刺激酵母细胞的生长，过表达p20导致酵母细胞生长缓慢。这些结果表明，p20是eIF 4 E活性的调节剂，其通过干扰eIF 4 E与eIF 4G的相互作用（例如，eIF 4F-复合物的形成）来抑制帽依赖性翻译起始。
In the yeast Saccharomyces cerevisiae a small protein named p20 is found associated with translation initiation factor eIF4E, the mRNA cap-binding protein. We demonstrate here that p20 is a repressor of cap-dependent translation initiation, p20 shows amino acid sequence homology to a region of eIF4G, the large subunit of the cap-binding protein complex eIF4F, which carries the binding site for eIF4E. Both, eIF4G and p20 bind to eIF4E and compete with each other for binding to eIF4E. The eIF4E-p20 complex can bind to the cap structure and inhibit cap-dependent but not cap-independent translation initiation: the translation of a mRNA with the 67 nucleotide Omega sequence of tobacco mosaic virus in its 5' untranslated region (which was previously shown to render translation cap-independent) is not inhibited by p20. Whereas the translation of the same mRNA lacking the Omega sequence is strongly inhibited by p20. Disruption of CAF20, the gene encoding p20, stimulates the growth of yeast cells, overexpression of p20 causes slower growth of yeast cells. These results show that p20 is a regulator of eIF4E activity which represses cap-dependent initiation of translation by interfering with the interaction of eIF4E with eIF4G, e.g. the formation of the eIF4F-complex.