通过控制细胞质53BP1的可用性,PLK1促进了线粒细胞监测途径
Matteo Burigotto1, Vincenza Vigorito1, Colin Gliech2
1Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, Trento, Italy.
波罗样酶1 (PLK1) 活性对于释放53BP1从kinetochores至关重要,使线粒细胞止时钟通路 (MSP) 能够监测细胞分裂时间并触发细胞周期停止.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 对DNA损伤的反应反应
背景情况:
- 53BP1蛋白参与DNA修复和p53介导的应激反应.
- 线性止时钟通路 (MSP) 使用53BP1,p53和USP28来监测细胞分裂时间并诱导细胞循环停止.
- MSP时间的确切机制尚不清楚.
研究的目的:
- 调查Polo样酶1 (PLK1) 在线性监测通路 (MSP) 中的作用.
- 为了确定53BP1.1的动态合器对接伙伴.
- 阐明MSP测量线粒体持续时间的机制.
主要方法:
- 抑制PLK1活动.
- 对53BP1局部化和与p53.3相互作用的分析.
- 通过免疫沉来识别53BP1的基内托科尔结合伙伴.
- 对CENP-F和53BP1结合的扰乱.
主要成果:
- PLK1的活性对于53BP1在线粒分裂过程中及时从kinetochores释放至关重要.
- 抑制PLK1导致53BP1在kinetochores中持续存在,从而损害了它与p53的细胞交互,并使MSP变得.
- 鉴定出CENP-F是53BP1.1的动态基因结合伙伴.
- 干扰53BP1-CENP-F相互作用并没有影响MSP介导的线粒分裂时间,这表明MSP不会在kinetochores上起作用.
结论:
- PLK1促进MSP,通过促进53BP1从kinetochores释放,产生p53相互作用所需的细胞结合池.
- 转基因持续时间是通过未知的细胞结合机制来测量的,而不是在基因.
- 这些发现促进了对细胞循环调节和DNA损伤反应途径的理解.
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