新型TORC1抑制剂Ecl1通过裂变酵母中的酸化来调节
Hokuto Ohtsuka1, Sawa Kawai1, Yurika Ito1
1Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Laboratory of Molecular Microbiology, Tokai National Higher Education and Research System, Nagoya University, Nagoya, Japan.
Aging cell
|February 6, 2025
概括
时间寿命延长器1 (Ecl1) 控制酵母菌中的细胞应激反应. Thr7酸化调节了Ecl1的功能,而Ecl1的数量抑制了TORC1,显示出双重调节模式.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 酵母遗传学 酵母遗传学
背景情况:
- 在裂变酵母中,延长时间寿命1 (Ecl1) 对细胞应激反应至关重要,包括饥饿.
- 已知ECL1抑制了拉巴胺素复合体1 (TORC1) 途径的标,但其翻译后的修饰仍然基本上没有特征.
研究的目的:
- 研究翻译后修改,特别是酸化对Ecl1调节和功能的影响.
- 阐明Ecl1酸化,应激反应和TORC1抑制之间的关系.
主要方法:
- 用质谱法分析了在硫或金属饥饿下酵母中ECL1酸化水平.
- 酸化模仿突变是为了评估Ecl1酸化在Thr7的功能后果而创建的.
- 共同免疫沉或类似的技术被用来研究ECL1和TORC1组件之间的物理相互作用.
主要成果:
- 质谱学确定了Thr7作为Ecl1上的酸化部位,在饥饿条件下水平下降.
- 在Thr7的酸化模仿突变损害了Ecl1在饥饿反应中的作用,表明酸化抑制了功能.
- Ecl1 抑制了TORC1 独立于Thr7 酸化状态,即使在酸化模仿突变的过度表达的情况下.
- 最近发现了Ecl1与TORC1子单元RAPTOR (Mip1) 之间的物理相互作用.
结论:
- Ecl1表现出双重的功能模式:TORC1的数量依赖抑制和Thr7的酸化依赖控制细胞功能.
- Thr7酸化作为Ecl1对细胞应激适应的贡献的负调节剂.
- Ecl1与RAPTOR (Mip1) 的相互作用为其TORC1抑制提供了一种机械联系.
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