Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs
Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs
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DOI：
10.1128/mcb.01298-07
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发表时间：
2008-01-01
影响因子：
5.3
通讯作者：
Willis, Anne E.
中科院分区：
文献类型：
--
作者：
Cobbold, Laura C.;Spriggs, Keith A.;Willis, Anne E.
原癌基因c-、L-和N-myc都可以通过内部核糖体进入的替代方法进行翻译，其中核糖体被招募到一个复杂的结构元件（内部核糖体进入段[IRES]）。核糖体的募集依赖于ires陷阱作用因子（ITAFs）的存在，ITAFs作为RNA的伴侣，允许mRNA获得正确的构象以与40S亚基相互作用。研究人员在这一领域面临的主要挑战之一是确定是否有ITAFs组调节ires介导的mrna亚群的翻译。我们已经鉴定出四种蛋白，分别为GRSF-1 （G-rich RNA sequence binding factor 1）、YB-1 （Y-box binding protein 1）、PSF （polypy嘧啶束结合蛋白相关剪接因子）及其结合伙伴p54nrb，它们与IRESs的myc家族结合。我们表明，这些蛋白在体内和体外积极调节Myc家族癌蛋白（c-， L-和N-Myc）的翻译。有趣的是，不相关的IRESs， BAG-1和Apaf-1的合成在体内不受YB-1， GRSF-1或PSF水平的影响，这表明这三种itaf是myc IRESs特异性的。Myc蛋白在细胞增殖中起作用；因此，这些结果对肿瘤发生的控制具有重要意义。
The proto-oncogenes c-, L-, and N-myc can all be translated by the alternative method of internal ribosome entry whereby the ribosome is recruited to a complex structural element (an internal ribosome entry segment [IRES]). Ribosome recruitment is dependent upon the presence of IRES-traps-acting factors (ITAFs) that act as RNA chaperones and allow the mRNA to attain the correct conformation for the interaction of the 40S subunit. One of the major challenges for researchers in this area is to determine whether there are groups of ITAFs that regulate the IRES-mediated translation of subsets of mRNAs. We have identified four proteins, termed GRSF-1 (G-rich RNA sequence binding factor 1), YB-1 (Y-box binding protein 1), PSF (polypyrimidine tract binding protein-associated splicing factor), and its binding partner, p54nrb, that bind to the myc family of IRESs. We show that these proteins positively regulate the translation of the Myc family of oncoproteins (c-, L-, and N-Myc) in vivo and in vitro. Interestingly, synthesis from the unrelated IRESs, BAG-1 and Apaf-1, was not affected by YB-1, GRSF-1, or PSF levels in vivo, suggesting that these three ITAFs are specific to the myc IRESs. Myc proteins play a role in cell proliferation; therefore, these results have important implications regarding the control of tumorigenesis.