TTK (Ab-676) Antibody

1. Treatment of a xenograft model of a CTNNB1-mutant cell line with the TTK inhibitor NTRC 0066-0 resulted in complete inhibition of tumor growth. Mutations in CTNNB1 are frequently observed in endometrial cancer and hepatocellular carcinoma, both of which exhibit elevated TTK expression. This suggests that mutant CTNNB1 may serve as a prognostic drug response biomarker, identifying patients most likely to benefit from TTK inhibition. PMID: 28751540
2. Lentiviral shRNA knockdown of TTK in several human liver cancer cell lines demonstrated its role in promoting cell growth and spreading, while simultaneously protecting against senescence and decreasing autophagy. In an experimental animal model, the in vitro knockdown of TTK effectively hindered the intrahepatic growth of human HCC xenografts. PMID: 27618777
3. The expression of TTK in gallbladder cancer (GBC) is lower than in normal tissues. Interestingly, higher levels of TTK expression in GBC are correlated with longer overall survival. PMID: 28883705
4. TTK is identified as a favorable prognostic biomarker associated with increased survival in triple-negative breast cancer. PMID: 27833085
5. Mps1 promotes checkpoint activation by sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and kinetochore-microtubule attachment, ensuring proper cell division. PMID: 28072388
6. Both monopolar spindle 1 (MPS1) and miR-21 depletion suppressed glioblastoma (GBM) cell proliferation, whereas, ectopic expression of miR-21 rescued GBM cell growth from MPS1 inhibition. PMID: 25991676
7. The TTK gene on 6q14.1 encodes a dual-specificity protein kinase (hMps1), a key spindle assembly checkpoint protein that regulates proper chromosomal alignment and segregation during mitosis. PMID: 28777004
8. Data show that Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is overexpressed in malignant mesothelioma (MM) and that its expression correlates with poor patient outcomes. PMID: 28759042
9. Distinct elements in the Mps1 N-terminal extension and tetratricopeptide repeat domains govern its localization to either the kinetochore or the centrosome. PMID: 27339139
10. Inhibition of the novel mitochondrial function Mps1 is sufficient to kill tumor cells. PMID: 27383047
11. Studies suggest that point mutations in the catalytic domain of MPS1 (C604Y and C604W) produce enzymes that retain catalytic activity but exhibit resistance to protein kinase inhibitors. These investigations analyzed crystal structures of recombinant wild-type and mutant MPS1 with various protein kinase inhibitors bound to the ATP-binding pocket of the catalytic domain. PMID: 28726638
12. TTK plays a critical role in preventing aneuploidy-induced cell death in pancreatic cancer. PMID: 28380042
13. HLF-mediated miR-132 directly suppresses TTK expression, thus exerting inhibitory effects on cancer cell proliferation, metastasis, and radioresistance. PMID: 27522003
14. Mps1 undergoes sumoylation, which plays an essential role in regulating its functions during mitosis. PMID: 26675261
15. Results suggest that monopolar spindle 1 kinase (MPS1) inhibition could be a viable therapeutic strategy for targeting tetraploid cancer cells. PMID: 26637805
16. Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. Overexpression of Cetn3 in cells attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, while depletion of Cetn3 leads to the formation of extra centrioles. PMID: 26354417
17. Knockdown of Cdkn3 stabilizes Mps1 at centrosomes. PMID: 26586430
18. TTK contributes to hepatocellular carcinoma tumorigenesis by promoting cell proliferation and migration. PMID: 26418879
19. Interaction of the central domain of ARHGEF17 with Mps1 has been observed. PMID: 26953350
20. Data show that TTK protein kinase (hMps1) interacts with proto-oncogene protein MDM2 both in vivo and in vitro. PMID: 26531827
21. Depletion of Mps1 reduces tumor cell viability compared to normal cells. PMID: 26398286
22. Mps1 plays a role in chromosome alignment by orchestrating Ndc80C-MT interactions. PMID: 26240331
23. High Mps1 expression, at both mRNA and protein levels, was found to be associated with high tumor grade, high Ki67 expression, and worse survival, particularly in Triple Negative Breast Cancer. PMID: 25731686
24. Data show five point mutations in the kinase domain of mitotic checkpoint kinase MPS1 that confer resistance against multiple inhibitors. PMID: 26202014
25. The N-terminal of Mps1 exhibits high sequence similarity to the classic NES. A fusion of this motif with EGFP results in dramatic exclusion of the fusion protein from the nucleus. PMID: 25886724
26. TTK was up-regulated in HCC specimens. Overexpression of TTK promoted cell proliferation, anchor-dependent colony formation, and resistance to sorafenib in HCC cells. PMID: 24905462
27. The dual-specificity protein kinase TTK, a key mitotic checkpoint regulator with links to p53 signaling, was further shown to be a promising overall prognostic marker for Hepatocellular carcinoma in a large patient cohort. PMID: 24859455
28. The checkpoint protein kinase monopolar spindle 1 (Mps1) directly bound to Ndc80C through two independent interactions. PMID: 26068854
29. The amino-terminal localization module of the spindle assembly checkpoint protein kinase MPS1 directly interacts with the HEC1 (highly expressed in cancer 1) calponin homology domain in the NDC80 (nuclear division cycle 80) kinetochore complex in vitro, in a phosphorylation-dependent manner. PMID: 26068855
30. Results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression. PMID: 25265012
31. Data suggest that MPS1 kinase inhibition could be a promising treatment strategy for pancreatic ductal adenocarcinoma (PDAC). PMID: 24282275
32. High TTK protein expression is associated with pancreatic cancer. PMID: 25137017
33. PP2A-B56 is a key phosphatase responsible for removing Mps1-mediated Knl1 phosphorylations, which are essential for Bub1/BubR1 recruitment in mammalian cells. PMID: 25246613
34. Findings suggest that high levels of Mps1 contribute to tumorigenesis by attenuating the spindle assembly checkpoint. PMID: 25063032
35. Our research provides evidence of a newly identified hMps1 phosphorylation site involved in the mitotic checkpoint, and that CHK2 contributes to chromosomal stability through hMps1. PMID: 24764296
36. Mps1 governs chromosomal organization during the early stages of mitosis to facilitate proper chromosome segregation. PMID: 24934155
37. MPS1 inhibitors may exhibit robust anticancer activity, either as standalone therapeutic interventions or in combination with microtubule-targeting chemicals. PMID: 23933817
38. Data show that TTK protein kinase, lymphocyte antigen 6 complex locus K, and insulin-like growth factor (IGF)-II mRNA binding protein 3 are tumor-associated antigens recognized by cytotoxic T lymphocytes and HLA-A24-restricted epitope peptides. PMID: 17784873
39. Sustained MPS1 activity is required for maintaining both the MAD1.C-MAD2 complex and open MAD2 (O-MAD2) at unattached kinetochores to facilitate C-MAD2 production. PMID: 24151075
40. A novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis has been discovered. PMID: 24187132
41. Two proteins that interact with BLM, RMI1 and RMI2, are phosphorylated upon SAC activation, and, like BLM, RMI1, and RMI2, are phosphorylated in an MPS1-dependent manner. PMID: 24108125
42. MPS1 is a protein kinase overexpressed in triple-negative breast cancer. PMID: 23700430
43. Mps1 is an acidophilic kinase with a striking tendency for phosphorylation of threonines. PMID: 23510141
44. Ultraviolet-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores. PMID: 23531678
45. Data propose that Chk1 and Mps1 jointly regulate Aurora-B, MCAK, Kif2b, and Hec1 to correct merotelic attachments, suggesting a role for Chk1 and Mps1 in error correction. PMID: 23321637
46. Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells. PMID: 23726842
47. A VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry. PMID: 23388454
48. Mps1 stimulates Aurora B recruitment to the centromere. PMID: 22732840
49. These data are consistent with a model in which Aurora B activity relieves a tetratricopeptide repeat domain-dependent inhibitory constraint on MPS1 localization. PMID: 23569217
50. We propose that persistent phosphorylation of Mps1 through BRAF(V600E) signaling is a key event in disrupting the control of centrosome duplication and chromosome stability, which may contribute to tumorigenesis. PMID: 22430208

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HGNC: 12401

OMIM: 604092

KEGG: hsa:7272

STRING: 9606.ENSP00000358813

UniGene: Hs.169840