FIGURE 3.
Bub1 activates SAC via interactions with multiple checkpoint proteins. The cartoon describes the interactions of Bub1 with Mad1, RZZ and Cdc20 in activating SAC signaling on unattached kinetochores. The left part shows a pair of chromatids with one kinetochore attached by microtubules and the other one unattached. The middle part shows recruiting Mad1/Mad2 onto kinetochores through two distinct and integrated pathways, Bub1-Mad1 and RZZ-Mad1. The dashed lines indicates dependency of RZZ on Bub1 and Mad1 on RZZ whereas the physical interactions have not been confirmed. RZZ binding with Mad1 promotes the binding between Bub1 and Mad1, which further catalyzes the formation of Mad2-Cdc20 complex as shown in the right part. Simultaneous interaction of Bub1 with Mad1-Mad2 and Cdc20 brings Mad2 close to Cdc20. The phosphorylation-mediated binding of the N-terminal Cdc20 with the C-terminal Mad1 exposes the Mad2 interacting motif on Cdc20 and facilitates the formation of Mad2-Cdc20 complex. The minor role of the kinase activity of Bub1 in SAC activation is not described here. Adapted from Lara-Gonzalez et al. (2021b).