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Monopolar spindle 1 (Mps1) kinase, also known as TTK protein kinase, is a mitotic kinase that is critical in the regulation of cell division, as it is involved in controlling the progression of cells through mitosis. It is widely found, but is not ubiquitous, in eukaryotes.
Monopolar spindle 1 (Mps1) kinase EC 188.8.131.52, also known as TTK protein kinase, is a mitotic kinase that is critical in the regulation of cell division, as it is involved in controlling the progression of cells through mitosis. It is widely found in eukaryotes and the C-terminal kinase domain is highly conserved.
In mammalian cells Mps1 kinase is localized at kinetochores, protein structures on chromatids to which the spindle microtubules attach. The enzyme is essential for the activation and maintenance of the spindle checkpoint, and along with Aurora B kinase acts to ensure that chromosomes are correctly attached to the mitotic spindle before cells can progress from metaphase to anaphase. It is therefore a crucial component of the checkpoint signaling pathway.
Mps1 kinase phosphorylates various components of the spindle pole body and influences, but is not crucial to, the duplication of the centrosome. The enzyme undergoes extensive autophosphorylation, which is essential for activation; it is primarily inactivated by degradation. Expression of Mps1 kinase is dysregulated in a variety of human cancers.
In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.