title: USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1.
abstract: Ubiquitin-specific protease 12 (USP12) plays a significant role in tumor cell apoptosis and cell cycle progression. However, the regulatory mechanism of USP12 in human cervical carcinoma HeLa cell growth is unknown. In this study, we showed that knockdown of USP12 effectively induced cell cycle arrest in HeLa cells and decreased BMI-1, c-Myc and cyclin D2 transcription levels. By contrast, unlike the inactive C48S mutant, over-expression of USP12 and the deubiquitinase activity enhanced L153S and R237C mutants, had the opposite effects. Interestingly, compared to wild-type, the L153S mutant resulted in a more effective cell cycle-promotion and increased BMI-1, c-Myc and cyclin D2 transcript levels. In addition to BMI-1, USP12 R237C exhibited a functional resemblance to the wild-type by involving c-Myc and cyclin D2. The effect of USP12 on HeLa cell apoptosis was not observed in our study. These results suggest that USP12 may be responsible for HeLa cell growth by affecting cell cycle progression.
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China. Electronic address: liyu322@126.com.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Tang
authors.affiliation: Department of Cardiac Surgery, The First Hospital of Shijiazhuang, 36 West Van Road, Shijiazhuang 050011, China. Electronic address: 805593762@qq.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang 050017, China. Electronic address: yingliliu2007@163.com.
authors.forename: Ying-Li
authors.initials: YL
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: wjmwjm_0103@163.com.
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. Electronic address: liudw56@tom.com.
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: tqb1980@hebmu.edu.cn.
authors.forename: Qing-Bao
authors.initials: QB
authors.lastname: Tian
mesh_terms: D002453:Cell Cycle; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C486402:USP12 protein, human; D063150:Polycomb Repressive Complex 1; D043222:Ubiquitin Thiolesterase
keywords: BMI-1; Cell cycle; Cyclin D2; HeLa cell; Ubiquitin-specific protease 12 (USP12); c-Myc