MALIGNANT TRANSFORMATION BY A EUKARYOTIC INITIATION-FACTOR SUBUNIT THAT BINDS TO MESSENGER-RNA 5' CAP
MALIGNANT TRANSFORMATION BY A EUKARYOTIC INITIATION-FACTOR SUBUNIT THAT BINDS TO MESSENGER-RNA 5' CAP
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DOI：
10.1038/345544a0
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发表时间：
1990-06-07
期刊：
影响因子：
64.8
通讯作者：
SONENBERG, N
中科院分区：
文献类型：
--
作者：
LAZARISKARATZAS, A;MONTINE, KS;SONENBERG, N
真核细胞mrna具有5'帽结构（m7GpppX），有助于与核糖体结合，是有效翻译所必需的1 - 3。一个特定的起始因子eIF-4F介导cap4 - 6的功能，由三个亚基组成7 - 10，其中一个亚基eIF-4E与cap结合。该亚基在细胞中的数量有限11 - 13，并且被认为受磷酸化调节12 - 16：各种处理后eIF-4E磷酸化的降低与细胞翻译率的降低相关。这些观察结果表明，eIF-4E位于有丝分裂信号转导通路上，我们推断，过表达eIF-4E可能会深刻影响细胞的生长特性。我们在此报告，在NIH 3T3和大鼠2成纤维细胞中，eIF-4E的过表达导致它们的致瘤性转化，这由三个标准决定：在单层细胞上形成转化灶；anchorage-independent增长;以及裸鼠体内的肿瘤形成。
EUKARYOTIC cellular mRNAs have a 5' cap structure (m7GpppX) that facilitates binding to ribosomes and is required for efficient translation1–3. A specific initiation factor, eIF-4F, mediates the function of the cap4–6and consists of three subunits7–10, one of which, eIF-4E, binds the cap. This subunit is present in limiting amounts in the cell11–13, and is thought to be regulated by phosphorylation12–16: decreased phosphorylation of eIF-4E following various treatments correlates with a decrease in cellular translation rate. These observations suggest that eIF-4E lies on the mitogenic signal transduction pathway, and we reasoned that overexpression of eIF-4E might profoundly affect cellular growth properties. We report here that overexpression of eIF-4E in NIH 3T3 and Rat 2 fibroblasts causes their tumorigenic transformation as determined by three criteria: formation of transformed foci on a monolayer of cells; anchorage-independent growth; and tumour formation in nude mice.