Figure 2.

A working model for RBX1 targeting. (A) In mouse embryos. RBX1 disruption in mouse induces early embryonic lethality due to reduced proliferation as a result of p27 accumulation. Simultaneous deletion of p27 restores cell proliferation and causes a partial rescue of embryonic death by extending the embryo's life from E6.5 to E9.5. It is unclear, at the present time, if abnormal DNA damage response is involved in later stage death of RBX1/p27 double null embryos. (B) In human cancer cells: RBX1 silencing triggers DNA damage response and checkpoint controls via modulating the levels of oncogenes or DNA replication proteins (DRPs), leading to activation of multiple cell killing pathways, including G2-M arrest, senescence and apoptosis.