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Mps1/TTK

Mps1 is an essential, dual-specificity kinase that functions as an important guardian of the fidelity of chromosome segregation. It is critical for the recruitment of SAC proteins to unattached kinetochores, mitotic checkpoint complex formation, and thus APC/C inhibition. Mps1 is also required for chromosome alignment and error correction. Inhibition of Mps1 activity causes cells to prematurely exit mitosis with unattached chromosomes, resulting in severe chromosome missegregation, aneuploidy, and ultimately cell death. Mps1 is expressed during mitosis in proliferating cells. Overexpression of Mps1 is observed in several human tumors, and correlates with worse prognosis. Further, Mps1 has been implicated in facilitating an aneuploidy-tolerant state in cancer cells. TTK is highly expressed in many types of tumors, including breast, lung and thyroid, etc. .Overexpression of Msp1/TTK promotes the proliferation of hepatocellular carcinoma cells via activating the AKT signaling pathway. In breast cancer patients, overexpression of Msp1/TTK correlates with increased grade and aggressiveness of breast cancers, which may involve with promoting the proliferation or survival of cancer cells.

References

1.Mason JM, et al. Proc Natl Acad Sci U S A. 2017;114(12):3127–3132.

Cell Cycle/DNA Damage

ABC(7) AChR(5) Antifolate(8) ATM/ATR(23) Aurora Kinase(37) CLK(15) c-Myc(16) DHFR(4) DNA Alkylator(29) DNA gyrase(7) DNA Repair Protein(21) DNA/RNA Synthesis(85) DNA-PK(11) GPR(19) HDAC(111) Hec1/Nek2(9) Integrin(38) LIM Kinase (LIMK)(4) Mps1/TTK(1) Nucleoside Antimetabolite/Analog(19) Other Targets(2) PARP(30) PLK(11) Potassium Channel(55) RAD51(1) Rho(5) ROCK(13) Telomerase(4) Topoisomerase(40) Wee1(2)