Galper Jasmin, Rayner Stephanie L, Hogan Alison L, Fifita Jennifer A, Lee Albert, Chung Roger S, Blair Ian P, Yang Shu
Centre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Centre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Int J Biochem Cell Biol. 2017 Aug;89:216-220. doi: 10.1016/j.biocel.2017.06.011. Epub 2017 Jun 24.
Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF. E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. By recognising and regulating the availability of several protein substrates, SCF plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. Cyclin F dysfunction has been implicated in various forms of cancer and CCNF mutations were recently linked to familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia, offering a new lead to understanding the pathogenic mechanisms underlying neurodegeneration. In this review, we evaluate the current literature on the function of cyclin F with an emphasis on its roles in cancer and neurodegeneration.
细胞周期蛋白F由CCNF编码,是Skp1-Cul1-F盒E3泛素连接酶复合物SCF的底物识别成分。E3泛素连接酶在泛素-蛋白酶体介导的蛋白质降解中起关键作用,这是细胞内蛋白质稳态机制的重要组成部分。通过识别和调节几种蛋白质底物的可用性,SCF在调节各种细胞过程中发挥作用,包括DNA的复制和修复以及细胞周期检查点控制。细胞周期蛋白F功能障碍与多种形式的癌症有关,最近CCNF突变与家族性和散发性肌萎缩侧索硬化症及额颞叶痴呆有关,为理解神经退行性变的致病机制提供了新线索。在本综述中,我们评估了目前关于细胞周期蛋白F功能的文献,重点是其在癌症和神经退行性变中的作用。