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Changes in the Level of Usp28 Deubiquitinase in the Cell Cycle of HCT116 Intestinal Adenocarcinoma Cells Indicate Its Functional Role in the Regulation of G 1 /S Transition
Cell and Tissue Biology Pub Date : 2020-09-24 , DOI: 10.1134/s1990519x20050065
V. M. Ryabov , E. N. Petrova , B. V. Popov

Abstract

Usp28 is a deubiquitinating enzyme that removes ubiquitin from its conjugates with substrates and prevents their degradation in proteasomes. Modern publications show that Usp28 and the Fbw7 ubiquitin ligase create a functional pair of proteins that controls ubiquitin-mediated degradation of key regulators of cellular functions, including Myc, Jun, Nicd, and Hif1. In this pair of proteins, Usp28 counteracts the destructive activity of Fbw7 and plays the role of a factor promoting tumor growth. Since the Usp28 targets are the Myc and Jun proteins associated with the cell cycle, we suggested that Usp28 regulates cell division and its level may change during the cell cycle. The aim of this work was to assess changes in the level of Usp28 during the cell cycle in HCT116 human intestinal carcinoma cells. HCT116 cells were synchronized by 72-h cultivation in a growth medium with a low serum content. In asynchronously dividing cells, the level of Usp28 was low and its localization was detected as nuclear–cytoplasmic. The general level of Usp28 and the degree of its nuclear localization increased in cells from the state of asynchronous growth to the late phase G1 followed by a decrease and redistribution of protein from the nucleus to the cytoplasm after the completion of phase G1. According to immunoblot data, the fluctuations in the levels of Usp28 and Cdc25A phosphatase in synchronized HCT116 cells in the cell cycle coincided. The immunofluorescence data directly corresponded to the results of immunoblotting. The results suggest that Usp28 can regulate the level and functional activity of the Cdc25A protein that controls the entry of cells into the DNA replication phase.



中文翻译:

HCT116肠腺癌细胞的细胞周期中Usp28去泛素酶水平的变化表明其在调控G 1 / S转变中的功能

摘要

Usp28是一种去泛素化酶,可从其与底物的结合物中去除泛素,并防止其在蛋白酶体中降解。现代出版物表明,Usp28和Fbw7泛素连接酶产生了一对功能蛋白,可控制泛素介导的细胞功能关键调节因子(包括Myc,Jun,Nicd和Hif1)的降解。在这对蛋白质中,Usp28抵消了Fbw7的破坏活性,并起促进肿瘤生长的作用。由于Usp28的靶标是与细胞周期相关的Myc和Jun蛋白,因此我们建议Usp28调节细胞分裂,其水平在细胞周期中可能会发生变化。这项工作的目的是评估HCT116人肠道癌细胞在细胞周期中Usp28水平的变化。通过在低血清含量的生长培养基中培养72 h,使HCT116细胞同步化。在异步分裂的细胞中,Usp28的水平较低,其定位被检测为核质。从细胞的异步生长到G期晚期,Usp28的一般水平及其核定位程度都在增加1期完成后,G 1期完成后蛋白质从细胞核减少并重新分布到细胞质。根据免疫印迹数据,在细胞周期中同步化的HCT116细胞中Usp28和Cdc25A磷酸酶水平的波动是一致的。免疫荧光数据直接对应于免疫印迹的结果。结果表明,Usp28可以调节Cdc25A蛋白的水平和功能活性,该蛋白控制细胞进入DNA复制阶段。

更新日期:2020-09-24
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