RETRACTED: Elevated tRNAiMet synthesis can drive cell proliferation and oncogenic transformation (Retracted article. See vol. 151, pg. 455, 2012)

被引:121
作者
Marshall, Lynne [1 ,2 ]
Kenneth, Niall S. [1 ]
White, Robert J. [1 ,2 ]
机构
[1] Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
[2] Garscube Estate, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland
关键词
D O I
10.1016/j.cell.2008.02.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Characteristics of transformed and tumor cells include increased levels of protein synthesis and elevated expression of RNA polymerase (pol) III products, such as tRNAs and 5S rRNA. However, whether deregulated pol III transcription contributes to transformation has been unclear. Generating cell lines expressing an inducible pol III-specific transcription factor, Brf1, allowed us to raise tRNA and 5S rRNA levels specifically. Brf1 induction caused an increase in cell proliferation and oncogenic transformation, whereas depletion of Brf1 impeded transformation. Among the gene products induced by Brf1 is the tRNA(i)(Met) that initiates polypeptide synthesis. Overexpression of tRNA(i)(Met) is sufficient to stimulate cell proliferation and allow immortalized fibroblasts to form foci in culture and tumors in mice. The data indicate that elevated tRNA synthesis can promote cellular transformation.
引用
收藏
页码:78 / 89
页数:12
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