Mps1 kinase functions in mitotic spindle assembly and error correction

HighlightsMps1 promotes mitotic checkpoint complex assembly and the establishment of bioriented chromosome attachment to spindle microtubules.Mps1 is a multidomain protein kinase that harbors protein motifs mediating its function in the SAC. These motifs are highly conserved during evolution, but with some important deviations that are species specific.The molecular description of Mps1 roles in SAC signaling and error correction has enhanced our understanding of the mechanisms that govern cell division. Defects in cell division result in gross chromosome segregation errors and genome instability.Inhibition of Mps1 catalytic activity to interfere with mitosis progression in tumor cells is a promising therapeutic window for the treatment of aggressive types of cancer.Mps1 may also be a suitable target for the treatment of infections caused by diverse pathogens, such as fungi.AbstractThe protein kinase Mps1 (also known as TTK) is a central component of the mitotic spindle assembly checkpoint (SAC), an essential self-monitoring system of the eukaryotic cell cycle that ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented on the mitotic spindle. Mps1 kinase is an important upstream regulator of the SAC and its recruitment to kinetochores critical for initiating SAC signaling. This review discusses the current understanding of Mps1 essential functions in the SAC, the emerging details of Mps1 role in error correction to safeguard genome stability, and the therapeutic potential of Mps1 inhibition for the treatment of cancer types associated with aberrant SAC signaling and chromosome segregation defects.