通过与核糖体结合,激活mTORC2
Vittoria Zinzalla1, Daniele Stracka, Wolfgang Oppliger
1Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Cell
|March 8, 2011
概括
核糖体,而不是蛋白质合成,对于哺乳动物的目标拉巴胺素复合体2 (mTORC2) 信号传输至关重要. 这种保守的mTORC2-核糖体相互作用对细胞生长和癌症进展至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 拉帕素 (TOR) 途径的目标是细胞生长和新陈代谢的中央调节者.
- 哺乳动物TOR复合体2 (mTORC2) 控制AGC激酶,并与癌症和糖尿病等疾病有关.
- 对于mTORC2活动的上游调节器的理解尚不完全.
研究的目的:
- 阐明mTORC2信号的上游调节机制.
- 调查核糖体和蛋白质合成在mTORC2激活中的作用.
- 为了确定mTORC2调节在正常和癌细胞中的生理相关性.
主要方法:
- 在酵母中进行遗传查.
- 研究哺乳动物细胞系,包括黑色素瘤和结肠癌细胞.
- 对mTORC2-核糖体关联和PI3K信号的分析.
主要成果:
- 核糖体,但不是蛋白质合成,是需要mTORC2信号.
- 活跃的mTORC2在物理上与核糖体结合.
- 胰岛素刺激的PI3K信号增强了mTORC2-核糖体结合.
- 在癌细胞中的瘤性PI3K信号传递中,mTORC2-核糖体关联是至关重要的.
结论:
- 核糖体直接激活了mTORC2.2. 这一过程.
- mTORC2-核糖体相互作用是mTORC2激活的保存机制.
- 这种调节机制确保了mTORC2活动与细胞生长能力有关.
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