title: The deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth.
abstract: 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.
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Functional Neurosurgery, Hebei General Hospital, Shijiazhuang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Tang
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China.
authors.forename: Dian-Wu
authors.initials: DW
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China. Electronic address: tianqingbao1980@aliyun.com.
authors.forename: Qing-Bao
authors.initials: QB
authors.lastname: Tian
mesh_terms: D019943:Amino Acid Substitution; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D056742:Cyclin D2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009857:Oncogenes; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
chemical_list: C069077:BMI1 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D063150:Polycomb Repressive Complex 1; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; C527170:Usp22 protein, human
keywords: Apoptosis; Cell cycle; Deubiquitinating enzyme activity; HeLa cell; Small interfering RNA; USP22