MALIGNANT TRANSFORMATION BY A EUKARYOTIC INITIATION-FACTOR SUBUNIT THAT BINDS TO MESSENGER-RNA 5' CAP

被引:849
作者
LAZARISKARATZAS, A [1 ]
MONTINE, KS [1 ]
SONENBERG, N [1 ]
机构
[1] MCGILL UNIV,MCGILL CANC CTR,MONTREAL H3G 1Y6,QUEBEC,CANADA
关键词
D O I
10.1038/345544a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
EUKARYOTIC cellular mRNAs have a 5' cap structure (m7 GpppX) that facilitates binding to ribosomes and is required for efficient translation1-3. A specific initiation factor, eIF-4F, mediates the function of the cap4-6 and 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. © 1990 Nature Publishing Group.
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页码:544 / 547
页数:4
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