The deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth

• Published in: Gene 2015-11, Vol.572 (1), p.49-56
• Main Authors: Liu, Ying-Li, Zheng, Jie, Tang, Li-Juan, Han, Wei, Wang, Jian-Min, Liu, Dian-Wu, Tian, Qing-Bao
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Apoptosis; Apoptosis - physiology; Cell cycle; Cell Cycle - physiology; Cell Proliferation - physiology; Cyclin D2 - metabolism; Deubiquitinating enzyme activity; Gene Knockdown Techniques; HeLa cell; HeLa Cells; Humans; Mutagenesis, Site-Directed; Mutation; Oncogenes; Polycomb Repressive Complex 1 - metabolism; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-myc - metabolism; RNA, Small Interfering - genetics; Signal Transduction; Small interfering RNA; Thiolester Hydrolases - antagonists & inhibitors; Thiolester Hydrolases - genetics; Thiolester Hydrolases - physiology; Tumor Suppressor Protein p53 - metabolism; Ubiquitin-Specific Proteases - antagonists & inhibitors; Ubiquitin-Specific Proteases - genetics; Ubiquitin-Specific Proteases - physiology; USP22
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2015.06.075

Ubiquitin-specific protease 22 (USP22) can regulate the cell cycle and apoptosis in many cancer cell types, while it is still unclear whether the deubiquitinating enzyme activity of USP22 is necessary for these processes. As little is known about the impact of USP22 on the growth of HeLa cell, we observed whether USP22 can effectively regulate HeLa cell growth as well as the necessity of deubiquitinating enzyme activity for these processes in HeLa cell. In this study, we demonstrate that USP22 can regulate cell cycle but not apoptosis in HeLa cell. The deubiquitinating enzyme activity of USP22 is necessary for this process as confirmed by an activity-deleted mutant (C185S) and an activity-decreased mutant (Y513C). In addition, the deubiquitinating enzyme activity of USP22 is related to the levels of BMI-1, c-Myc, cyclin D2 and p53. Our findings indicate that the deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth, and it promotes cell proliferation via the c-Myc/cyclin D2, BMI-1 and p53 pathways in HeLa cell. •USP22 down-regulation can affect cell cycle but not apoptosis.•USP22 promotes cell proliferation via the c-Myc/cyclin D2, BMI-1 and p53 pathways.•The deubiquitin enzyme activity is necessary for the regulatory effect.