Altmann M, Schmitz N, Berset C, Trachsel H
Institute for Biochemistry and Molecular Biology, University of Bern, Switzerland.
EMBO J. 1997 Mar 3;16(5):1114-21. doi: 10.1093/emboj/16.5.1114.
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.
在酿酒酵母中，发现一种名为p20的小蛋白与翻译起始因子eIF4E（mRNA帽结合蛋白）相关联。我们在此证明p20是帽依赖性翻译起始的抑制因子。p20与eIF4G（帽结合蛋白复合物eIF4F的大亚基）的一个区域显示出氨基酸序列同源性，该区域携带eIF4E的结合位点。eIF4G和p20都能与eIF4E结合，并相互竞争与eIF4E的结合。eIF4E - p20复合物能够结合帽结构并抑制帽依赖性而非帽非依赖性的翻译起始：5'非翻译区带有烟草花叶病毒67个核苷酸ω序列的mRNA（先前已证明其翻译不依赖帽）的翻译不受p20抑制。而缺少ω序列的相同mRNA的翻译则受到p20的强烈抑制。编码p20的基因CAF20的破坏会刺激酵母细胞的生长，p20的过表达会导致酵母细胞生长缓慢。这些结果表明，p20是eIF4E活性的调节因子，它通过干扰eIF4E与eIF4G的相互作用（例如eIF4F复合物的形成）来抑制帽依赖性的翻译起始。
