TOR通过PKA和叉头转录因子FHL1调节核糖体蛋白基因表达
Dietmar E Martin1, Alexandre Soulard, Michael N Hall
1Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Cell
|December 29, 2004
概括
拉巴胺素 (TOR) 途径的标通过蛋白激酶A (PKA) 调节核糖体生物发生. 这项研究确定了叉头样转录因子1 (FHL1) 和其辅因子IFH1和CRF1作为这种营养敏感信号机制的关键参与者.
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:
- 核糖体生物发生对于细胞生长至关重要,并且受到环境因素的严格调节.
- 拉帕素 (TOR) 信号通路的营养敏感标是细胞生长的中心调节者.
- TOR影响蛋白激酶A (PKA) 局部化,但其对核糖体蛋白 (RP) 基因调节的下游转录因子仍未确定.
研究的目的:
- 阐明转录因子通过酵母中的TOR-PKA通路调节RP基因.
- 揭示了将环境传感与核糖体生物发生控制联系起来的信号机制.
主要方法:
- 酵母遗传学和分子生物学技术.
- 对转录因子局部化和活性进行分析.
- 对RP基因促进体中的蛋白质-蛋白质相互作用的研究.
主要成果:
- 叉头样转录因子FHL1,以及联合激活剂IFH1和核心压缩剂CRF1,对于TOR/PKA介导的RP基因转录至关重要.
- 通过PKA传递TOR信号,抑制YAK1激酶的活性,并在细胞质中保留CRF1.
- 通过与IFH1竞争FHL1结合,TOR失活导致YAK1激活,CRF1酸化,核积累,并随后抑制RP基因转录,从而与IFH1竞争FHL1结合.
结论:
- 描述了一种新的信号通路,通过TOR/PKA连接环境传感与核糖体生物生成的调节.
- FHL1,IFH1,CRF1和YAK1之间的相互作用提供了一个控制RP基因表达的机制,以响应营养的可用性.
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