The Role And Molecular Mechanism Of Ubiquitin Specific Peptidase 14 In Regulating CDK1 Ubiquitination In Breast Cancer

Breast cancer is the most common malignant tumor among women in China,which seriously threatens women's physical and mental health.It has become a major public health problem in the current society.Tumorogenesis is closely related to the dysregulation of cell cycle.Cell cycle progression is one of the basic processes of cell life activities.Cell cycle can be divided into interphase and dividing phase(M phase),and the interphase can further be divided into G1,S and G2 phases.Cyclin-dependent protein kinase 1(CDK1)is a key protein driving cells from G2 phase to M phase.However,the degradation mechanisms of CDK1,especially its deubiquitination,is still unclear.In our study,we found knocking down USP14 could inhibit the proliferation of breast cancer cells and arrested the cell cycle at G2/M phase.Further Co-IP studies demonstrated that ubiquitin-specific peptidase 14 could interact with CDK1.Altering the expression of USP14 affected the protein level of CDK1 while the mRNA level was unaffected,indicating that USP14 affected the stability of CDK1.Based on the deubiquitination function of USP14,we detected the ubiquitination level of CDK1 by disturbing the function of USP14.IU-1(USP14 specific inhibitor)treatment or USP14 knockdown significantly increased the ubiquitination level of CDK1 accompanied with decreased expression of CDK1 protein.In conclusion,our research demonstrated that USP14 could regulate the cycle of breast cancer cells by regulating the ubiquitination of CDK1,which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.