APC/C-CDH1抑制AROS介导的保护,防止DNA损伤诱导的衰老通过ubiquitination
Ji-Hye Yang1, Hanbyeul Choi1, Seung Baek Lee2
1Department of Molecular Biology, Dankook University, Cheonan 31116, Korea.
BMB reports
|September 8, 2025
概括
活跃SIRT1调节器 (AROS) 与APC2结合,抑制细胞循环调节器Cyclin B1的破坏. APC/C-CDH1降解AROS,抑制DNA损伤引起的衰老,揭示了相互调节的作用.
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:
- 亚纳酶促进复合体/循环体 (APC/C) 是细胞循环的关键调节者,通过无处化控制蛋白质降解.
- 管理APC/C活动及其精确监管的机制仍然不完全理解.
研究的目的:
- 阐明控制APC/C活动的监管机制.
- 研究SIRT1活性调节剂 (AROS) 在APC/C功能和细胞衰老中的作用.
主要方法:
- 同免疫沉降测定以确认蛋白质相互作用 in vivo.
- 分析AROS,APC11和APC2之间的蛋白质结合竞争.
- 评估B1环素降解的情况.
- 通过CDH1.1对AROS无化和降解的研究.
- 评估CDH1对AROS介导的保护对DNA损伤引起的衰老的影响.
主要成果:
- AROS与APC2直接相互作用,这是APC/C的催化子单元.
- 对APC2的AROS结合阻碍了环林B1.1的泛化和随后的破坏.
- 该APC/C协作激活剂CDH1在D-box依赖的方式在AROS上进行ubiquitinates和降解.
- CDH1对抗AROS对抗DNA损伤引起的衰老的保护作用.
结论:
- 通过竞争APC2结合,AROS作为APC/C活动的负调节剂,从而稳定Cyclin B1.
- CDH1相互调节AROS稳定性,将APC/C活动与衰老控制联系起来.
- 这些发现揭示了一个新的调控轴,涉及AROS和APC/C-CDH1在管理DNA损伤引起的衰老.
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