keyword
MENU ▼
Read by QxMD icon Read
search

Spindle assembly checkpoint targets

keyword
https://www.readbyqxmd.com/read/27819146/mps1-ttk-a-novel-target-and-biomarker-for-cancer
#1
Yuan Xie, Anqiang Wang, Jianzhen Lin, Liangcai Wu, Haohai Zhang, Xiaobo Yang, Xueshuai Wan, Ruoyu Miao, Xinting Sang, Haitao Zhao
Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits...
December 1, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27810909/the-ubiquitin-ligase-crl2zyg11-targets-cyclin-b1-for-degradation-in-a-conserved-pathway-that-facilitates-mitotic-slippage
#2
Riju S Balachandran, Cassandra S Heighington, Natalia G Starostina, James W Anderson, David L Owen, Srividya Vasudevan, Edward T Kipreos
The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase is known to target the degradation of cyclin B1, which is crucial for mitotic progression in animal cells. In this study, we show that the ubiquitin ligase CRL2(ZYG-11) redundantly targets the degradation of cyclin B1 in Caenorhabditis elegans and human cells. In C. elegans, both CRL2(ZYG-11) and APC/C are required for proper progression through meiotic divisions. In human cells, inactivation of CRL2(ZYG11A/B) has minimal effects on mitotic progression when APC/C is active...
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27713168/the-aurora-kinase-a-inhibitor-tc-a2317-disrupts-mitotic-progression-and-inhibits-cancer-cell-proliferation
#3
Yoo Hong Min, Wootae Kim, Ja-Eun Kim
Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27633003/mps1-kinase-as-a-potential-therapeutic-target-in-medulloblastoma
#4
Irina Alimova, June Ng, Peter Harris, Diane Birks, Andrew Donson, Michael D Taylor, Nicholas K Foreman, Sujatha Venkataraman, Rajeev Vibhakar
Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27623074/infrank-a-ranking-based-identification-of-influential-genes-in-biological-networks
#5
Xiuliang Cui, Xiaofeng Li, Jin Li, Xue Wang, Wen Sun, Zhuo Cheng, Jin Ding, Hongyang Wang
Capturing the predominant driver genes is critical in the analysis of high-throughput experimental data; however, existing methods scarcely include the unique characters of biological networks. Herein we introduced a ranking-based computational framework (inFRank) to rank the proteins by their influence. Using inFRank, we identified the top 20 influential genes in hepatocellular carcinoma (HCC). Network analysis revealed a prominent community composed of 7 influential genes. Intriguingly, five genes among the community were critical for mitotic spindle assembly checkpoint (SAC), suggesting that dysregulation of SAC could be a distinct feature of HCC and targeting SAC-associated genes might be a promising therapeutic strategy...
September 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27540016/the-novel-tubulin-binding-checkpoint-activator-bal101553-inhibits-eb1-dependent-migration-and-invasion-and-promotes-differentiation-of-glioblastoma-stem-like-cells
#6
Raphael Berges, Aurélie Tchoghandjian, Stephane Honore, Marie-Anne Esteve, Dominique Figarella-Branger, Felix Bachmann, Heidi A Lane, Diane Braguer
Glioblastoma (GBM) patients have limited treatment options. Cancer stem-like cells (CSLCs) contribute to GBM invasiveness and repopulation; hence, they represent promising targets for novel therapies. BAL101553 is a prodrug of BAL27862, a novel microtubule-destabilizing agent inhibiting tumor cell proliferation through activation of the Spindle Assembly Checkpoint, which is currently in Phase 1/2 clinical development. Broad anti-cancer activity has been demonstrated against human cancer models, including tumors refractory to conventional treatments...
August 18, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27524485/ccan-assembly-configures-composite-binding-interfaces-to-promote-cross-linking-of-ndc80-complexes-at-the-kinetochore
#7
Gülsah Pekgöz Altunkaya, Francesca Malvezzi, Zuzana Demianova, Tomasz Zimniak, Gabriele Litos, Florian Weissmann, Karl Mechtler, Franz Herzog, Stefan Westermann
Partitioning of the genome requires kinetochores, large protein complexes that mediate dynamic attachment of chromosomes to the spindle. Kinetochores contain two supramolecular protein assemblies. The ten-protein KMN network harbors key microtubule-binding sites in the Ndc80 complex and mediates assembly of checkpoint complexes via the KNL-1/Spc105 protein [1, 2]. As KMN does not contact DNA directly, it relies on different centromere-binding proteins for recruitment and cell-cycle-dependent assembly. These proteins are collectively referred to as the CCAN (constitutive centromere-associated network) [2-4]...
September 12, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27512141/inhibition-of-bcl-xl-sensitizes-cells-to-mitotic-blockers-but-not-mitotic-drivers
#8
Ailsa Bennett, Olivia Sloss, Caroline Topham, Louisa Nelson, Anthony Tighe, Stephen S Taylor
Cell fate in response to an aberrant mitosis is governed by two competing networks: the spindle assembly checkpoint (SAC) and the intrinsic apoptosis pathway. The mechanistic interplay between these two networks is obscured by functional redundancy and the ability of cells to die either in mitosis or in the subsequent interphase. By coupling time-lapse microscopy with selective pharmacological agents, we systematically probe pro-survival Bcl-xL in response to various mitotic perturbations. Concentration matrices show that BH3-mimetic-mediated inhibition of Bcl-xL synergises with perturbations that induce an SAC-mediated mitotic block, including drugs that dampen microtubule dynamics, and inhibitors targeting kinesins and kinases required for spindle assembly...
August 2016: Open Biology
https://www.readbyqxmd.com/read/27435760/spindle-assembly-checkpoint-as-a-potential-target-in-colorectal-cancer-current-status-and-future-perspectives
#9
Vânia Diogo, Joana Teixeira, Patrícia M A Silva, Hassan Bousbaa
Colorectal cancer (CRC), one of the most common malignancies worldwide, is often diagnosed at an advanced stage, and resistance to chemotherapeutic and existing targeted therapy is a major obstacle to its successful treatment. New targets that offer alternative clinical options are therefore urgently needed. Recently, perturbation of the spindle assembly checkpoint (SAC), the surveillance mechanism that maintains anaphase inhibition until all chromosomes reach the metaphase plate, has been regarded as a promising target to fight cancer cells, either alone or in combination regimens...
June 23, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/27383047/mps1-kinase-regulates-tumor-cell-viability-via-its-novel-role-in-mitochondria
#10
X Zhang, Y Ling, Y Guo, Y Bai, X Shi, F Gong, P Tan, Y Zhang, C Wei, X He, A Ramirez, X Liu, C Cao, H Zhong, Q Xu, R Z Ma
Targeting mitotic kinase monopolar spindle 1 (Mps1) for tumor therapy has been investigated for many years. Although it was suggested that Mps1 regulates cell viability through its role in spindle assembly checkpoint (SAC), the underlying mechanism remains less defined. In an endeavor to reveal the role of high levels of mitotic kinase Mps1 in the development of colon cancer, we unexpectedly found the amount of Mps1 required for cell survival far exceeds that of maintaining SAC in aneuploid cell lines. This suggests that other functions of Mps1 besides SAC are also employed to maintain cell viability...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27378817/fatostatin-inhibits-cancer-cell-proliferation-by-affecting-mitotic-microtubule-spindle-assembly-and-cell-division
#11
Ankur A Gholkar, Keith Cheung, Kevin J Williams, Yu-Chen Lo, Shadia A Hamideh, Chelsea Nnebe, Cindy Khuu, Steven J Bensinger, Jorge Z Torres
The sterol regulatory element-binding protein (SREBP) transcription factors have become attractive targets for pharmacological inhibition in the treatment of metabolic diseases and cancer. SREBPs are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SREBP cleavage-activating protein (SCAP), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion, and migration, and it arrests cancer cells in G2/M phase...
August 12, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27339139/modular-elements-of-the-tpr-domain-in-the-mps1-n-terminus-differentially-target-mps1-to-the-centrosome-and-kinetochore
#12
Joseph R Marquardt, Jennifer L Perkins, Kyle J Beuoy, Harold A Fisk
Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27325694/phosphorylation-of-astrin-regulates-its-kinetochore-function
#13
Hee Jin Chung, Ji Eun Park, Nam Soo Lee, Hongtae Kim, Chang-Young Jang
The error-free segregation of chromosomes, which requires the precisely timed search and capture of chromosomes by spindles during early mitotic and meiotic cell division, is responsible for genomic stability and is achieved by the spindle assembly checkpoint in the metaphase-anaphase transition. Mitotic kinases orchestrate M phase events, such as the reorganization of cell architecture and kinetochore (KT) composition with the exquisite phosphorylation of mitotic regulators, to ensure timely and temporal progression...
August 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27317434/usp9x-stabilizes-xiap-to-regulate-mitotic-cell-death-and-chemoresistance-in-aggressive-b-cell-lymphoma
#14
Katharina Engel, Martina Rudelius, Jolanta Slawska, Laura Jacobs, Behnaz Ahangarian Abhari, Bettina Altmann, Julia Kurutz, Abirami Rathakrishnan, Vanesa Fernández-Sáiz, Andrä Brunner, Bianca-Sabrina Targosz, Felicia Loewecke, Christian Johannes Gloeckner, Marius Ueffing, Simone Fulda, Michael Pfreundschuh, Lorenz Trümper, Wolfram Klapper, Ulrich Keller, Philipp J Jost, Andreas Rosenwald, Christian Peschel, Florian Bassermann
The mitotic spindle assembly checkpoint (SAC) maintains genome stability and marks an important target for antineoplastic therapies. However, it has remained unclear how cells execute cell fate decisions under conditions of SAC-induced mitotic arrest. Here, we identify USP9X as the mitotic deubiquitinase of the X-linked inhibitor of apoptosis protein (XIAP) and demonstrate that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons. We find that primary human aggressive B-cell lymphoma samples exhibit high USP9X expression that correlate with XIAP overexpression...
2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27308561/sustaining-the-spindle-assembly-checkpoint-to-improve-cancer-therapy
#15
Roberta Visconti, Rosa Della Monica, Domenico Grieco
To prevent chromosome segregation errors, the spindle assembly checkpoint (SAC) delays mitosis exit until proper spindle assembly. We found that the FCP1 phosphatase and its downstream target WEE1 kinase oppose the SAC, promoting mitosis exit despite malformed spindles. We further showed that targeting this pathway might be useful for cancer therapy.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27239782/prevalence-of-germline-mutations-in-the-spindle-assembly-checkpoint-gene-bub1b-in-individuals-with-early-onset-colorectal-cancer
#16
Marc-Manuel Hahn, Lilian Vreede, Sonja A S A Bemelmans, Erica van der Looij, Ad Geurts van Kessel, Hans K Schackert, Marjolijn J L Ligtenberg, Nicoline Hoogerbrugge, Roland P Kuiper, Richarda M de Voer
Germline mutations in BUB1B, encoding BUBR1, one of the crucial components of the spindle assembly checkpoint (SAC), have been shown to cause variable phenotypes, including the recessive mosaic variegated aneuploidy (MVA) syndrome, which predisposes to cancer. Reduced levels of the wild-type BUBR1 protein have been linked to the development of gastrointestinal neoplasms. To determine whether mutations in BUB1B are enriched in individuals with colorectal cancer (CRC), we performed amplicon-based targeted next-generation sequencing of BUB1B on germline DNA of 192 individuals with early-onset CRC (≤50 years)...
November 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27213315/antiproliferative-fate-of-the-tetraploid-formed-after-mitotic-slippage-and-its-promotion-a-novel-target-for-cancer-therapy-based-on-microtubule-poisons
#17
REVIEW
Yuji Nakayama, Toshiaki Inoue
Microtubule poisons inhibit spindle function, leading to activation of spindle assembly checkpoint (SAC) and mitotic arrest. Cell death occurring in prolonged mitosis is the first target of microtubule poisons in cancer therapies. However, even in the presence of microtubule poisons, SAC and mitotic arrest are not permanent, and the surviving cells exit the mitosis without cytokinesis (mitotic slippage), becoming tetraploid. Another target of microtubule poisons-based cancer therapy is antiproliferative fate after mitotic slippage...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27191586/identification-of-a-mutation-causing-a-defective-spindle-assembly-checkpoint-in-high-ethyl-caproate-producing-sake-yeast-strain-k1801
#18
Tetsuya Goshima, Ryo Nakamura, Kazunori Kume, Hiroki Okada, Eri Ichikawa, Hiroyasu Tamura, Hirokazu Hasuda, Masaaki Inahashi, Naoto Okazaki, Takeshi Akao, Hitoshi Shimoi, Masaki Mizunuma, Yoshikazu Ohya, Dai Hirata
In high-quality sake brewing, the cerulenin-resistant sake yeast K1801 with high ethyl caproate-producing ability has been used widely; however, K1801 has a defective spindle assembly checkpoint (SAC). To identify the mutation causing this defect, we first searched for sake yeasts with a SAC-defect like K1801 and found that K13 had such a defect. Then, we searched for a common SNP in only K1801 and K13 by examining 15 checkpoint-related genes in 23 sake yeasts, and found 1 mutation, R48P of Cdc55, the PP2A regulatory B subunit that is important for the SAC...
August 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27177088/characterization-of-the-novel-indolylmaleimides-pda-66-and-pda-377-effect-on-canine-lymphoma-cells
#19
Wen Liu, Julia Beck, Laura C Schmidt, Catrin Roolf, Anahit Pews-Davtyan, Barbara C Rütgen, Sabine Hammer, Saskia Willenbrock, Anett Sekora, Arndt Rolfs, Matthias Beller, Bertram Brenig, Ingo Nolte, Christian Junghanss, Ekkehard Schütz, Hugo Murua Escobar
Protein kinase inhibitors are widely used in chemotherapeutic cancer regimens. Maleimide derivatives such as SB-216763 act as GSK-3 inhibitor targeting cell proliferation, cell death and cell cycle progression.Herein, the two arylindolylmaleimide derivatives PDA-66 and PDA-377 were evaluated as potential chemotherapeutic agents on canine B-cell lymphoma cell lines. Canine lymphoma represents a naturally occurring model closely resembling the human high-grade non-Hodgkin's lymphoma (NHL). PDA-66 showed more pronounced effects on both cell lines...
June 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27134171/slx5-slx8-promotes-replication-stress-tolerance-by-facilitating-mitotic-progression
#20
Yee Mon Thu, Susan Kaye Van Riper, LeeAnn Higgins, Tianji Zhang, Jordan Robert Becker, Todd William Markowski, Hai Dang Nguyen, Timothy Jon Griffin, Anja Katrin Bielinsky
Loss of minichromosome maintenance protein 10 (Mcm10) causes replication stress. We uncovered that S. cerevisiae mcm10-1 mutants rely on the E3 SUMO ligase Mms21 and the SUMO-targeted ubiquitin ligase complex Slx5/8 for survival. Using quantitative mass spectrometry, we identified changes in the SUMO proteome of mcm10-1 mutants and revealed candidates regulated by Slx5/8. Such candidates included subunits of the chromosome passenger complex (CPC), Bir1 and Sli15, known to facilitate spindle assembly checkpoint (SAC) activation...
May 10, 2016: Cell Reports
keyword
keyword
92900
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"