Figure 2.

Regulation and biological functions. RBX1 and RBX2 are induced upon growth signals, whereas RBX2 is also induced by various stresses, including ROS, TPA, and hypoxia. While both are required for mouse embryonic development, RBX1 or RBX2 forms SCF E3 ubiquitin ligases by complexing with their respective cullins. Following cullin neddylation, RBX1-SCFs and RBX2-SCFs are activated to promote the growth and survival of cancer cells. MLN4924, a small molecule inhibitor of NAE, blocks cullin neddylation to inactivate SCFs, leading to the induction of apoptosis and senescence, thus acting as a novel class of anticancer drugs.