在正常发育和癌症中对eIF4E剂量的差异要求
Morgan L Truitt1, Crystal S Conn1, Zhen Shi2
1Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell
|June 23, 2015
概括
细胞启动因子4E (eIF4E) 的50%降低通过限制特定mRNAs的翻译来阻碍癌细胞转化. 癌细胞劫持过多的eIF4E用于瘤发生.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞启动因子4E (eIF4E) 是主要的帽子结合蛋白.
- 它在生物体翻译剂量中的作用尚未完全理解.
- eIF4E与癌症的发展有关.
研究的目的:
- 为了研究生物对eIF4E剂量的要求.
- 了解eIF4E水平在细胞转化和瘤发生中的作用.
主要方法:
- 生成一个Eif4e哈普洛因不足小鼠模型.
- 全基因组翻译分析. 全基因组翻译分析.
- 在瘤转化过程中对mRNA翻译的分析.
主要成果:
- 在eIF4E (haploinsufficiency) 中减少50%并没有影响正常发育或全球蛋白质合成.
- 减少eIF4E显著损害了细胞转化.
- eIF4E剂量对于转化具有特定5' UTRs的mRNAs至关重要,它们参与了反应性氧物种调节.
- 这种转化程序在体内推动了癌细胞的生存.
结论:
- eIF4E水平超过正常发育的水平.
- 癌细胞利用高的eIF4E驱动一个支持瘤发生的转化程序.
- 向eIF4E剂量为癌症提供了潜在的治疗策略.
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