CDC123是一种ATPase,通过调节eIF2复杂组合组合来调节mRNA翻译和综合应激反应
Anthony L Erb1, Sara K Young-Baird2
1Department of Biochemistry and Molecular Biology, Uniformed Services University, Bethesda, MD, 20814; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, 20817.
The Journal of biological chemistry
|December 29, 2025
概括
综合应激反应 (ISR) 影响翻译,但CDC123是一个协助eIF2生物发生的陪伴者,是一种新的ISR调节器. 功能受损的CDC123活动会影响eIF2的组装和翻译,这表明CDC123是ISR相关疾病的治疗点.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 综合应激反应 (ISR) 对于细胞平衡至关重要,它调节全球和mRNA特定的翻译.
- 对ISR的调节失调与各种疾病状态有关.
- 压力感应激酶通过控制真核细胞翻译启动因子2 (eIF2) 复合物的活性来调节翻译.
研究的目的:
- 确定综合应激反应 (ISR) 的新型调节剂.
- 调查伴侣CDC123在eIF2生物发生和ISR调制中的作用.
- 探索CDC123作为ISR相关疾病的潜在治疗点.
主要方法:
- 研究了CDC123在eIF2复杂组装和功能中的作用.
- 利用遗传和药理学策略来调节CDC123的活动.
- 研究了受损CDC123在ISR激活期间对转化控制和细胞结局的影响.
- 研究了CDC123介导的eIF2组合的机制,包括通过ATP水解的潜在调节.
主要成果:
- 确定了CDC123作为ISR的新型调节剂,促进eIF2生物发生.
- 证明受损的CDC123活动会破坏eIF2复杂组合,通过非正规途径导致ISR相关的翻译缺陷.
- 表明药理或遗传干预可以挽救这些翻译缺陷.
- 提供了证据表明,CDC123介导的eIF2组件可以通过ATP水解来调节.
结论:
- CDC123在eIF2生物发生和mRNA翻译调节中发挥着重要作用.
- CDC123代表了与ISR失调相关的疾病的潜在治疗标.
- 阐明了对eIF2异体体形成及其调节的新型机制性见解.
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