keyword
MENU ▼
Read by QxMD icon Read
search

MPS1

keyword
https://www.readbyqxmd.com/read/29805692/mps1-is-associated-with-the-braf-v600e-mutation-but-does-not-rely-on-the-classic-ras-raf-mek-erk-signaling-pathway-in-thyroid-carcinoma
#1
Yike Li, Yanyan Zhang, Shuaishuai Xiao, Pengzhou Kong, Caixia Cheng, Ruyi Shi, Fang Wang, Ling Zhang, Juan Wang, Zhiwu Jia, Shuai Wu, Yun Liu, Jiansheng Guo, Xiaolong Cheng, Yongping Cui, Jing Liu
In previous studies, the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation has been identified in multiple malignant tumors. BRAFV600E has been revealed to contribute to tumorigenesis by the activation of phospho-mitogen-activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho-MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction-direct sequencing...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29764757/synthesis-and-profiling-of-a-3-aminopyridin-2-one-based-kinase-targeted-fragment-library-identification-of-3-amino-5-pyridin-4-yl-pyridin-2-1h-one-scaffold-for-monopolar-spindle-1-mps1-and-aurora-kinases-inhibition
#2
Daren Fearon, Isaac M Westwood, Rob L M van Montfort, Richard Bayliss, Keith Jones, Vassilios Bavetsias
Screening a 3-aminopyridin-2-one based fragment library against a 26-kinase panel representative of the human kinome identified 3-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2(1H)-one (2) and 3-amino-5-(pyridin-4-yl)pyridin-2(1H)-one (3) as ligand efficient inhibitors of the mitotic kinase Monopolar Spindle 1 (MPS1) and the Aurora kinase family. These kinases are well recognised as attractive targets for therapeutic intervention for treating cancer. Elucidation of the binding mode of these fragments and their analogues has been carried out by X-ray crystallography...
April 17, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29736010/mps1-inhibitors-synergise-with-low-doses-of-taxanes-in-promoting-tumour-cell-death-by-enhancement-of-errors-in-cell-division
#3
Ana Rita R Maia, Simon Linder, Ji-Ying Song, Chantal Vaarting, Ute Boon, Colin E J Pritchard, Arno Velds, Ivo J Huijbers, Olaf van Tellingen, Jos Jonkers, René H Medema
BACKGROUND: Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, and indeed Mps1 inhibitors synergise with the spindle poison docetaxel in inhibiting the growth of tumours in mice. METHODS: To investigate how the combination of docetaxel and a Mps1 inhibitor (Cpd-5) promote tumour cell death, we treated mice transplanted with BRCA1-/- ;TP53-/- mammary tumours with docetaxel and/or Cpd-5...
May 8, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29731963/aurora-b-prevents-premature-removal-of-spindle-assembly-checkpoint-proteins-from-the-kinetochore-a-key-role-for-aurora-b-in-mitosis
#4
Mark D Gurden, Simon J Anderhub, Amir Faisal, Spiros Linardopoulos
Accurate chromosome segregation is dependent on the spindle assembly checkpoint (SAC). In current models, the key direct role of Aurora B in the SAC has been suggested to be to promote rapid kinetochore localisation of MPS1, allowing MPS1 to generate the checkpoint signal. However, Aurora B is also thought to play an indirect role in the SAC through the destabilisation of kinetochore-microtubule (KT-MT) attachments. Here, we demonstrate that Aurora B activity is not required for the kinetochore recruitment of the majority of SAC proteins...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29610759/molecular-signature-of-the-imprintosome-complex-at-the-mating-type-locus-in-fission-yeast
#5
Célia Raimondi, Bernd Jagla, Caroline Proux, Hervé Waxin, Serge Gangloff, Benoit Arcangioli
Genetic and molecular studies have indicated that an epigenetic imprint at mat1 , the sexual locus of fission yeast, initiates mating type switching. The polar DNA replication of mat1 generates an imprint on the Watson strand. The process by which the imprint is formed and maintained through the cell cycle remains unclear. To understand better the mechanism of imprint formation and stability, we characterized the recruitment of early players of mating type switching at the mat1 region. We found that the switch activating protein 1 (Sap1) is preferentially recruited inside the mat1M allele on a sequence ( SS13 ) that enhances the imprint...
January 16, 2018: Microbial Cell
https://www.readbyqxmd.com/read/29502948/mps1-phosphorylates-its-n-terminal-extension-to-relieve-autoinhibition-and-activate-the-spindle-assembly-checkpoint
#6
Guillaume Combes, Helena Barysz, Chantal Garand, Luciano Gama Braga, Ibrahim Alharbi, Philippe Thebault, Luc Murakami, Dominic P Bryne, Stasa Stankovic, Patrick A Eyers, Victor M Bolanos-Garcia, William C Earnshaw, John Maciejowski, Prasad V Jallepalli, Sabine Elowe
Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC...
March 19, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29491436/unattached-kinetochores-drive-their-own-capturing-by-sequestering-a-clasp
#7
Caroline Kolenda, Jennifer Ortiz, Marina Pelzl, Sarina Norell, Verena Schmeiser, Johannes Lechner
Kinetochores that are not attached to microtubules prevent chromosome missegregation via the spindle assembly checkpoint. We show that they also promote their own capturing. Similar to what governs the localization of spindle assembly checkpoint proteins, the phosphorylation of Spc105 by Mps1 allows unattached kinetochores to sequester Stu1 in cooperation with Slk19. The withdrawal of Stu1, a CLASP essential for spindle integrity, from microtubules and attached kinetochores disrupts the organization of the spindle and thus allows the enhanced formation of dynamic random microtubules that span the nucleus and are ideal to capture unattached kinetochores...
February 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29380674/identification-of-the-hot-spot-residues-for-pyridine-derivative-inhibitor-cct251455-and-atp-substrate-binding-on-monopolar-spindle-1-mps1-kinase-by-molecular-dynamic-simulation
#8
Kai Chen, Wenxiu Duan, Qianqian Han, Xuan Sun, Wenqian Li, Shuangyun Hu, Jiajia Wan, Jiang Wu, Yushu Ge, Dan Liu
Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay...
March 8, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29378962/disruption-of-the-anaphase-promoting-complex-confers-resistance-to-ttk-inhibitors-in-triple-negative-breast-cancer
#9
K L Thu, J Silvester, M J Elliott, W Ba-Alawi, M H Duncan, A C Elia, A S Mer, P Smirnov, Z Safikhani, B Haibe-Kains, T W Mak, D W Cescon
TTK protein kinase (TTK), also known as Monopolar spindle 1 (MPS1), is a key regulator of the spindle assembly checkpoint (SAC), which functions to maintain genomic integrity. TTK has emerged as a promising therapeutic target in human cancers, including triple-negative breast cancer (TNBC). Several TTK inhibitors (TTKis) are being evaluated in clinical trials, and an understanding of the mechanisms mediating TTKi sensitivity and resistance could inform the successful development of this class of agents. We evaluated the cellular effects of the potent clinical TTKi CFI-402257 in TNBC models...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29237818/mps1-promotes-chromosome-meiotic-chromosome-biorientation-through-dam1
#10
Régis E Meyer, Jamin Brown, Lindsay Beck, Dean S Dawson
In budding yeast meiosis, homologous chromosomes become linked by chiasmata and then move back and forth on the spindle until they are bioriented, with the kinetochores of the partners attached to microtubules from opposite spindle poles. Certain mutations in the conserved kinase, Mps1, result in catastrophic meiotic segregation errors but mild mitotic defects. We tested whether Dam1, a known substrate of Mps1, was necessary for its critical meiotic role. We found that kinetochore-microtubule attachments are established even when Dam1 is not phosphorylated by Mps1, but that Mps1 phosphorylation of Dam1 sustains those connections...
February 15, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29162720/direct-interactions-of-mitotic-arrest-deficient-1-mad1-domains-with-each-other-and-mad2-conformers-are-required-for-mitotic-checkpoint-signaling
#11
Wenbin Ji, Yibo Luo, Ejaz Ahmad, Song-Tao Liu
As a sensitive signaling system, the mitotic checkpoint ensures faithful chromosome segregation by delaying anaphase onset even when a single kinetochore is unattached to mitotic spindle microtubules. The key signal amplification reaction for the checkpoint is the conformational conversion of "open" mitotic arrest deficient 2 (O-MAD2) into "closed" MAD2 (C-MAD2). The reaction has been suggested to be catalyzed by an unusual catalyst, a MAD1:C-MAD2 tetramer, but how the catalysis is executed and regulated remains elusive...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29100415/the-e2f-activators-control-multiple-mitotic-regulators-and-maintain-genomic-integrity-through-sgo1-and-bubr1
#12
Miyoung Lee, Yainyrette Rivera-Rivera, Carlos S Moreno, Harold I Saavedra
The E2F1, E2F2, and E2F3a transcriptional activators control proliferation. However, how the E2F activators regulate mitosis to maintain genomic integrity is unclear. Centrosome amplification (CA) and unregulated spindle assembly checkpoint (SAC) are major generators of aneuploidy and chromosome instability (CIN) in cancer. Previously, we showed that overexpression of single E2F activators induced CA and CIN in mammary epithelial cells, and here we show that combined overexpression of E2F activators did not enhance CA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29078282/rad52-phosphorylation-by-ipl1-and-mps1-contributes-to-mps1-kinetochore-localization-and-spindle-assembly-checkpoint-regulation
#13
Gyubum Lim, Won-Ki Huh
Rad52 is well known as a key factor in homologous recombination. Here, we report that Rad52 has functions unrelated to homologous recombination in Saccharomyces cerevisiae ; it plays a role in the recruitment of Mps1 to the kinetochores and the maintenance of spindle assembly checkpoint (SAC) activity. Deletion of RAD52 causes various phenotypes related to the dysregulation of chromosome biorientation. Rad52 directly affects efficient operation of the SAC and accurate chromosome segregation. Remarkably, by using an in vitro kinase assay, we found that Rad52 is a substrate of Ipl1/Aurora and Mps1 in yeast and humans...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28982702/phosphatase-regulated-recruitment-of-the-spindle-and-kinetochore-associated-ska-complex-to-kinetochores
#14
Sushama Sivakumar, Gary J Gorbsky
Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska) complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28947820/mps1-kinase-dependent-sgo2-centromere-localisation-mediates-cohesin-protection-in-mouse-oocyte-meiosis-i
#15
Warif El Yakoubi, Eulalie Buffin, Damien Cladière, Yulia Gryaznova, Inés Berenguer, Sandra A Touati, Rocío Gómez, José A Suja, Jan M van Deursen, Katja Wassmann
A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region...
September 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28943088/bubr1-promotes-bub3-dependent-apc-c-inhibition-during-spindle-assembly-checkpoint-signaling
#16
Katharina Overlack, Tanja Bange, Florian Weissmann, Alex C Faesen, Stefano Maffini, Ivana Primorac, Franziska Müller, Jan-Michael Peters, Andrea Musacchio
The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif ("loop") of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets...
October 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28851706/dna-damage-induces-a-kinetochore-based-atm-atr-independent-sac-arrest-unique-to-the-first-meiotic-division-in-mouse-oocytes
#17
Simon I R Lane, Stephanie L Morgan, Tianyu Wu, Josie K Collins, Julie A Merriman, Elias ElInati, James M Turner, Keith T Jones
Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on activation of the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes of DNA damage checkpoint proteins are assembled at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min...
October 1, 2017: Development
https://www.readbyqxmd.com/read/28840249/a-kinase-phosphatase-network-that-regulates-kinetochore-microtubule-attachments-and-the-sac
#18
Giulia Vallardi, Marilia Henriques Cordeiro, Adrian Thomas Saurin
The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore. It integrates the activities of two kinases (MPS1 and Aurora B) and two phosphatases (PP1 and PP2A-B56) to regulate kinetochore-microtubule attachments and the spindle assembly checkpoint (SAC). We will first discuss each of these enzymes separately, to describe how they are regulated at kinetochores and why this is important for their primary function in controlling either microtubule attachments or the SAC...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28821799/plk1-bound-to-bub1-contributes-to-spindle-assembly-checkpoint-activity-during-mitosis
#19
Masanori Ikeda, Kozo Tanaka
For faithful chromosome segregation, the formation of stable kinetochore-microtubule attachment and its monitoring by the spindle assembly checkpoint (SAC) are coordinately regulated by mechanisms that are currently ill-defined. Here, we show that polo-like kinase 1 (Plk1), which is instrumental in forming stable kinetochore-microtubule attachments, is also involved in the maintenance of SAC activity by binding to Bub1, but not by binding to CLASP2 or CLIP-170. The effect of Plk1 on the SAC was found to be mediated through phosphorylation of Mps1, an essential kinase for the SAC, as well as through phosphorylation of the MELT repeats in Knl1...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806765/pka-activity-is-essential-for-relieving-the-suppression-of-hyphal-growth-and-appressorium-formation-by-mosfl1-in-magnaporthe-oryzae
#20
Yang Li, Xue Zhang, Shuai Hu, Huiquan Liu, Jin-Rong Xu
In the rice blast fungus Magnaporthe oryzae, the cAMP-PKA pathway regulates surface recognition, appressorium turgor generation, and invasive growth. However, deletion of CPKA failed to block appressorium formation and responses to exogenous cAMP. In this study, we generated and characterized the cpk2 and cpkA cpk2 mutants and spontaneous suppressors of cpkA cpk2 in M. oryzae. Our results demonstrate that CPKA and CPK2 have specific and overlapping functions, and PKA activity is essential for appressorium formation and plant infection...
August 2017: PLoS Genetics
keyword
keyword
110062
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"