The Molecular Mechanism Of Deubiquitinase USP14 In Regulating Cell Cycle Progression Of Breast Cancer

Breast cancer is one of the most major threats to women globally.The abnormal proliferation is one of the hallmarks of breast cancer.The rapid progression of cell cycle is the basis of tumor cell proliferation.Elucidating the molecular mechanism of cell cycle regulation in tumor cells is one of great significances for understanding the occurrence and development of cancer and the development of anti-tumor drugs.Cyclin-dependent kinase 1(CDK1)is one of the key kinases for cells entering from G2 phase to M phase during cell cycle progression.However,little is known about the degradation mechanisms of CDK1.USP14 is one of the main proteasome-associated deubiquitinating enzymes which is critical for proteome homeostasis,and plays an important role in the initiation and progression of cancer.In this study,we found that USP14 showed a high expression in breast cancer cells and promoted the proliferation of cancer cells.Through flow cytometry,we found that USP14 inhibition arrested the cell cycle at G2/M phase.Further studies demonstrated that USP14 affected the expression and protein homeostasis of CDK1.Besides,USP14 could also interacted with CDK1.As USP14 is a deubiquitinase,we detected the effect of USP14 on the ubiquitination of CDK1.The results revealed that USP14 stabilized CDK1 by deubiquitinating the K48-linked ubiquitination.In conclusion,our findings revealed an indispensable role of USP14 in regulating the stability of CDK1 and the cell cycle progression of breast cancer,suggesting that USP14 might be a potential therapeutic target against breast cancer.