抑制 Myc 致癌活性,由核糖体蛋白脱不充分症抑制
Maria Barna1, Aya Pusic, Ornella Zollo
1Department of Biochemistry & Biophysics, University of California San Francisco, Rock Hall Room 384C, 1550 Fourth Street, San Francisco, California 94158-2517, USA. maria.barna@ucsf.edu
Nature
|November 18, 2008
概括
我的瘤基因增强蛋白质合成,增加细胞大小和加速癌症. 恢复正常的蛋白质合成抑制了Myc.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- Myc瘤基因控制蛋白质合成机制,影响细胞生长和癌症的发展.
- 提高蛋白质合成能力在癌症进展中的确切作用尚不清楚.
研究的目的:
- 调查恢复正常蛋白质合成如何影响Myc驱动的瘤发生.
- 阐明将Myc,蛋白质合成和癌症启动联系在一起的分子机制.
主要方法:
- 利用核糖体蛋白异构细胞小鼠在Emu-Myc/+转基因小鼠中使蛋白质合成正常化.
- 评估细胞大小,细胞周期进展,编程细胞死亡和转化控制.
- 研究了上限依赖和内部核糖体入口部位 (IRES) 依赖的翻译之间的切换.
主要成果:
- 恢复正常的蛋白质合成抑制了Myc的致癌潜力,减少了细胞大小和循环加速.
- 当蛋白质合成正常化时,过度表达的癌前细胞显示细胞死亡率增加.
- Myc过度激活影响了转化转换到依赖IRES的翻译,影响了Cdk11表达,线粒细胞进展和基因组稳定性.
结论:
- 提高蛋白质合成直接增加细胞大小,加速细胞循环的进展,有助于Myc的致癌潜力.
- 在Myc过度激活下游的异常cap-dependent翻译特别损害了IRES-dependent翻译,导致基因组不稳定.
- 恢复精确的翻译控制抑制了基因组的不稳定性,突出了它在癌症发病中的关键作用.
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