Mitotic checkpoint protein (SAC)

Mitotic checkpoint proteins are a group of evolutionarily conserved components that together form the *spindle assembly checkpoint* (SAC), a signaling system guarding chromosome segregation during cell division. Their collective function is to ensure that daughter cells inherit the correct chromosome complement by blocking anaphase onset until all chromosomes are properly attached to the spindle apparatus. Key proteins include Mad1, Mad2, Bub1, BubR1, Bub3, Mps1, and Cdc20, which assemble at unattached kinetochores and generate a “wait anaphase” signal largely by inhibiting the anaphase-promoting complex/cyclosome (APC/C), an essential E3 ubiquitin ligase. Dysfunction in these proteins disrupts chromosome segregation fidelity, contributing to diverse conditions, most notably cancer, where chromosomal instability and aneuploidy drive disease initiation and progression. Several mitotic checkpoint proteins and their regulators have become therapeutic targets for the development of anticancer drugs, particularly spindle poisons and newer kinase inhibitors. Targeting this network poses safety challenges due to the risk of compromising the fidelity of genome transmission in all dividing cells **Note:** For structured or mechanistic pharmacological analysis, use of specific individual protein targets (e.g., “Mitotic arrest deficient protein 2” for Mad2) is recommended instead of the plural/generic form. Otherwise, "Mitotic checkpoint protein" (singular) or "Mitotic checkpoint complex" is the most canonical form for describing the checkpoint as a drug target family.

Other names

Spindle assembly checkpoint proteinsSpindle checkpoint proteinsMitotic checkpoint complex proteinsSAC proteinsMad1Mad2Bub1Bub3BubR1/Mad3Mps1Cdc20CENP-EZW10 complex

Stabilization or destabilization of microtubules (promotes persistence of unattached kinetochores and checkpoint activation, as with Paclitaxel, vincristine, etc.). Pharmacologic inhibition of kinase components (e.g., Mps1 inhibitors silence the checkpoint signal and force mitotic exit with unaligned chromosomes). Kinase inhibition (GSK3 inhibition weakens checkpoint effectiveness; Mps1 inhibition interrupts checkpoint activation).