USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1

• Inhibition of USP12 enzyme activity blocks HeLa cell cycle.
• Enhancement of USP12 catalytic activity promotes HeLa cell cycle.
• Regulation of HeLa cell cycle by USP12 may be linked with c-Myc, cyclin D2 and BMI-1.

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.