The spindle assembly checkpoint: Molecular mechanisms and kinase-targeted drug discovery
Inês Lima, Fernanda Borges, António Pombinho, Daniel Chavarria
Abstract
The spindle assembly checkpoint (SAC) is a surveillance mechanism required for the fidelity of chromosome segregation, ensuring that anaphase is not initiated until all chromosomes are properly attached to the mitotic spindle. In cancer cells, SAC inactivation leads to aneuploidy beyond the cell's adaptation, culminating in cell death. This review provides a concise overview of the SAC signaling process and properties. Recent drug discovery strategies to selectively target kinases, particularly Aurora B and monopolar spindle kinase (MPS1), aimed at developing innovative anticancer agents able to override SAC are also presented.
Topics & Concepts
Drug discoveryDrugSpindle checkpointComputational biologyChemistryPharmacologyBiologyBiochemistryKinetochoreGeneChromosomeMicrotubule and mitosis dynamicsCancer-related Molecular PathwaysUbiquitin and proteasome pathways