Fig. 6: RCC1 knockdown induces G1 arrest in cervical cancer cells.

a RCC1 protein levels were measured by Western blot in HeLa and SiHa cells. b Western blot analysis of E2F1, Cdk1, and Cdk2 protein levels in SiHa cells transfected with RCC1 siRNAs. c Flow cytometry of SiHa cells transfected with RCC1 siRNAs for 24 h and treated with bleomycin for 36 h. d Flow cytometry of SiHa cells transfected with RCC1 siRNAs for 48 h, then stained with anti-BrdU and 7-AAD. e A model depicting the E7/c-Jun/RCC1 pathway. In this model, E7 binds to and degrades Rb and releases E2F1 from the pRb-E2F1 complex. E7 also upregulates c-Jun, allowing c-Jun to bind to the RCC1 promoter and increase its transcriptional activation. Increased RCC1 upregulates the steady-state levels of E2F1, likely through the proteasome pathway. Moreover, RCC1 positively regulates the steady-state levels of E7 oncoprotein, which in turn promotes E2F1. Cdk1, a target of E2F1, plays a role in G1/S progression in the presence of Cdk2. This E7/c-Jun/RCC1/E2F1/Cdk1 pathway may lead to abrogation of the G1 checkpoint in the presence of damaged DNA, resulting in dysregulation of the G1/S cell cycle. Data representative of three biological replicates are shown. *P < 0.05; **P < 0.01