Fig. 5

DDB2 mediated proteolysis of CDT2 may corelated with prognostic in cancer patients. a DDB2 promoted CDT2 proteolysis in Chang liver and CCC-HPF-1 cells. Chang liver and CCC-HPF-1 cells were treated with siRNAs of luciferase and DDB2 for 48 h, and harvested for Western blot. PCNA was taken as loading control. The relative protein levels of CDT2, CDT1 and DDB2 were normalized and plotted on the right panel. ** Denoted P < 0.01; *** denoted P < 0.001, and the error bars indicated SD. b CCC-HPF-1 cells were arrested in G1 phase after DDB2 silencing. FACS analysis of DNA contents in CCC-HPF-1 cells after treatment with siRNAs of luciferase and DDB2 for 48 h. c Expression of CDT2 and DDB2 in ovarian teratoma and breast cancer tissues detected by IHC. Scale bar: 50 µm and 100 µm. d The schematic model of CRL4^DDB2 ubiquitin ligase regulates DNA replication initiation through degrading CDT2. In late M and G1 phase, the degradation of CDT2 mediated by CRL4^DDB2 ubiquitin ligase stabilizes CDT1. Accumulation of CDT1 promotes recruitment of MCMs onto origins and assembly of pre-replication complex