保存的Hsp70酸化调节了DNA损伤后的细胞周期进展
Thomas Moss1,2, Alexandra Wooldredge1,2, Koustav Bhakta1,2
1G.W. Hooper foundation, University of California at San Francisco, San Francisco, USA.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
热冲击蛋白70 (Hsp70) 在T495的酸化在DNA损伤过程中发生内源性. 这种保守的修饰调节了细胞周期的进展,并延迟了细胞分裂,揭示了基本的细胞生物学见解.
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:
- 热冲击蛋白70 (Hsp70) 作为一个分子伴侣.
- 翻译后的修改调节了Hsp70的活动.
- 病原体激酶可以针对Hsp70进行抑制.
研究的目的:
- 在人类细胞中研究Hsp70在T495的内源酸化.
- 了解Hsp70酸化对DNA损伤的反应中的作用.
- 阐明Hsp70酸化影响细胞循环进展的机制.
主要方法:
- 在人体细胞中使用质谱学研究内源性Hsp70酸化.
- 使用了具有相仿和素Hsp70变体的酵母模型.
- 进行生物化学测试以分析Hsp70构成和基质结合.
主要成果:
- 在T495的Hsp70酸化在DNA损伤期间在人类细胞内源性发生,特别是当基切割修复受到压力时.
- 这种修改是细胞周期依赖的.
- 在酵母中,在T495模仿或缺乏酸化的Hsp70变体在正常和破坏DNA的条件下破坏G1/S细胞周期进展.
- T495E突变导致开放式的Hsp70形状,而不会阻碍基质结合.
结论:
- 在T495的动态Hsp70酸化是一种调节G1/S过渡的保守机制.
- Hsp70酸化延迟了细胞循环的进展,以应对DNA损伤.
- 来自病原体与宿主相互作用的洞察力可以揭示细胞生物学的基本原则.
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