• Plant cells form acentrosomal spindles with microtubules (MTs) converged toward two structurally undefined poles by employing MT minus end-directed Kinesin-14 motors. (figshare.com)
  • Here we combine the first large-scale serial electron tomography of whole mitotic spindles in early C. elegans embryos with live-cell imaging to reconstruct all microtubules in 3D and identify their plus- and minus-ends. (nature.com)
  • We classify them as kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to their positions, and quantify distinct properties of each class. (nature.com)
  • Remarkably, despite the high turnover of microtubules throughout mitosis 2 , the spindle maintains its bipolar structure with the chromosomes at its center and two poles that are separated by the plane of cell division. (nature.com)
  • In all spindles, the microtubule cytoskeleton connects to chromosomes via a special class of microtubules called kinetochore microtubules (KMTs). (nature.com)
  • In order to explain this behavior, we polymerized microtubules in vitro and we used kinesin motors to show integration with nanotube s and manipulation of functional biohybrid assemblies. (cdc.gov)
  • Microtubules assemble into mitotic spindles, while the kinesin motors are responsible for microtubule-based transport and cellular division. (cdc.gov)
  • Eg5 is localized at the centrosomes, spindle microtubules, and intracellular bridge. (biolegend.com)
  • somes is performed by the mitotic spindle, a cellular machine composed of microtubules and their associated proteins. (colorado.edu)
  • Spindles are built from microtubules, which have biochemically distinct plus and minus ends. (colorado.edu)
  • Specialized sites on the chromosomes called kinetochores attach to spindle microtubules, and these kinetochore-microtubule attachments are necessary for proper chromosome segregation. (colorado.edu)
  • Kinetochore capture by spindle microtubules and the subsequent chromosome movements occur via highly dynamic microtubules that maintain kinetochore attachment during significant microtubule turnover. (colorado.edu)
  • Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. (ens-lyon.fr)
  • Kinesins are a protein superfamily that function via microtubules by converting energy released from ATP hydrolysis into mechanical work. (nottingham.ac.uk)
  • T. brucei Kinesin-13s Kin13-1, -3 (both 13A) and -6 (13C) interactions with microtubules were observed in vitro. (nottingham.ac.uk)
  • Kin13-3 depolymerises microtubules, consistent with the functions of other Kinesin-13A members. (nottingham.ac.uk)
  • Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. (umbc.edu)
  • Reduced Klp3a function results in disorganized interpolar microtubules and shortened spindles. (ncsu.edu)
  • Normally, acentric poleward segregation occurs at the periphery of the spindle in association with interpolar microtubules. (ncsu.edu)
  • In klp3a mutants, acentrics fail to localize and segregate along the peripheral interpolar microtubules and are abnormally positioned in the spindle interior. (ncsu.edu)
  • During mitosis , chromosomes establish connections to mitotic spindle microtubules (MTs) via specialized protein complexes, called kinetochores, and subsequently translocate to the midzone of the bipolar spindle. (axonmedchem.com)
  • The nanotube bundles are similar to the potential of nanotubes to induce genetic damage size of microtubules that form the mitotic spindle in normal lung cells, cultured primary and immor- and may be incorporated into the mitotic spindle talized human airway epithelial cells were apparatus. (cdc.gov)
  • Although intact cortices, kinetochore MTs, and midzone augmentation are dispensable, this patronin-based change in ipMT minus-end dynamics is sufficient to induce the elongation of spindles capable of separating chromosomes. (escholarship.org)
  • The mitotic spindle ensures the faithful segregation of chromosomes. (nature.com)
  • In toto , our results show that the connection between centrosomes and chromosomes is mediated by an anchoring into the entire spindle network and that any direct connections through KMTs are few and likely very transient. (nature.com)
  • The mitotic spindle is a dynamic microtubule-based apparatus that ensures the segregation of chromosomes during cell division. (nature.com)
  • If the role of KMTs is to mediate forces between chromosomes and spindle poles, they need to somehow connect to the centrosomes. (nature.com)
  • To segregate the chromosomes faithfully during cell division, cells assemble a spindle that captures the kinetochores and pulls them towards opposite poles. (divide-eunetwork.org)
  • At kinetochore-microtubule plus ends, the kinesin-8 family member Kif18A is essential to align mitotic chromosomes at the spindle equator during cell division, but how it accomplishes this function is unclear. (nih.gov)
  • We are working to understanding how the mitotic spindle organizes and moves chromosomes. (colorado.edu)
  • During mitosis, spindle structure and movement dictates how chromosomes will be separated and act as the sole mechanism for even distribution of these chromosomes. (unm.edu)
  • During mitosis, chromosomes are connected to a microtubule-based spindle. (ens-lyon.fr)
  • Our results strongly suggest that an outward forcegenerated by the spindle midzone, independently of centrosomes, is sufficient tosegregate chromosomes in mitotic cells. (ens-lyon.fr)
  • The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. (oncotarget.com)
  • Anaphase B spindle elongation contributes to chromosome segregation during Drosophila melanogaster embryo mitosis. (escholarship.org)
  • Indeed, that such forces exist in C. elegans is evidenced by the maintenance of half-spindle lengths throughout mitosis 5 and in many perturbations experiments. (nature.com)
  • We found that the relative concentration of the kinesin-14 family protein Pkl1 is decreased in meiosis I compared to mitosis, while the concentration of the kinesin-5 family protein Cut7 remains constant. (divide-eunetwork.org)
  • Inhibition of NEK6 can lead to the termination of mitosis, chromatin spindle defects, and abnormal chromosomal differentiation [ 5 - 7 ]. (hindawi.com)
  • Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein, a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. (adooq.com)
  • Monastrol blocks mitosis (IC5N/A = 14 μM) by binding to the mitotic kinesin Eg5, a motor protein required for spindle bipolarity. (adooq.com)
  • Litronesib is a selective mitosis-specific kinesin Eg5 inhibitor, with antitumor activity. (adooq.com)
  • Our findings suggest that kinesin-8 family members have developed biochemically distinct activities throughout evolution and have implications for how Kif18A affects kinetochore-microtubule plus-end dynamics during mitosis in animal cells. (nih.gov)
  • Recent projects have focused on the contributions of kinesin-8 motor proteins to chromosome movements, and kinetochore capture in early mitosis. (colorado.edu)
  • The first of these is Bod1, a protein conserved throughout metazoans that associates with a large macromolecular complex and localizes with kinetochores and spindle poles during mitosis. (rupress.org)
  • Furthermore, cells with chromosomal instability appear to arrest in mitosis and form multipolar spindles upon Kif18A knockdown. (uvm.edu)
  • Based on these data, Kif18A may serve as a novel therapeutic target for aggressive, chromosomally unstable cancers because of its role in regulating mitotic spindle dynamics to promote successful progression through mitosis. (uvm.edu)
  • Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. (umbc.edu)
  • To date, it is unclear whether the convergent bipolar MT array assumes unified poles in plant spindles, and if so, how such a goal is achieved. (figshare.com)
  • Concomitantly, spindle poles became perfectly focused as if there were centrosome-like MT-organizing centers where ATK1 and ATK5 were highly enriched and at which kinetochore fibers pointed. (figshare.com)
  • These results led to the conclusion that the two Kinesin-14A motors formed oligomeric motor complexes that drove MT translocation toward the spindle pole to establish acentrosomal spindles with convergent poles. (figshare.com)
  • In this paper, we present evidence that anaphase B is induced by the minus end-stabilizing protein patronin, which antagonizes the kinesin-13 depolymerase KLP10A at spindle poles, thereby switching off the depolymerization of the minus ends of outwardly sliding ipMTs to suppress flux. (escholarship.org)
  • It interferes with chromosome alignment and overrides spindle assembly checkpoint and also Inhibits the recruitment of Mad1, Mad2 and centromere protein E (CENP-E) to kinetochores. (adooq.com)
  • The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
  • It also plays important roles in mitotic spindle formation and cytokinesis. (umbc.edu)
  • The first volume gathers reviews of many classes of drugs of contemporary interest for cancer therapy and is devoted to small molecules inhibitors of various proteins involved in cancer development such as Casein kinase 2 (CK2), Protein kinase B (PKB), mTOR, Hsp90, P-glycoprotein (P-gp), Kinesin spindle protein (KSP), Cyclooxygenase 2 (COX-2), Histone deacetylase enzymes (HDACs) and Topoisomerase I. (benthambooks.com)
  • Synthesis and Biological Evaluation of Optimized Inhibitors of the Mitotic Kinesin Kif18A. (axonmedchem.com)
  • The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. (oncotarget.com)
  • Here we demonstrate that kinesin motor protein Kif18A has the potential to serve as a minimally toxic target for the treatment of cancers such as triple negative breast cancer (TNBC) and colorectal cancer (CRC). (uvm.edu)
  • Background: Kinesin family member 18A ( KIF18A ) is involved in the development of a variety of human malignancies. (aging-us.com)
  • Recombinant Kinesin Family, Member 18A ( KIF18A ) belongs to Recombinant Kinesin Family [ 9 ], which is highly expressed in tumors and associated with poor prognosis [ 10 , 11 ]. (aging-us.com)
  • The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. (axonmedchem.com)
  • The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. (axonmedchem.com)
  • To understand how the two functionally redundant Kinesin-14A motors contributed to the spindle assembly, we had ATK1-GFP and ATK5-GFP fusion proteins expressed in their corresponding null mutants and found that they were functionally comparable to their native forms. (figshare.com)
  • also known as Eg5 or KIF11) is a Kinesin-5 subfamily member and has been the focus of a significant drug development effort throughout the pharmaceutical industry for the last 15 years. (cytoskeleton.com)
  • Eg5 (also known as kinesin-like protein KIF11, kinesin-related motor protein Eg5, kinesin-like spindle protein HKSP, and thyroid receptor interacting protein 5 (TRIP5)) is a 119 kD kinesin-like protein family, BimC subfamily. (biolegend.com)
  • Human KIF12 was investigated as a representative of Kinesin-16 whilst the roles of Kinesin-13 subfamilies A and C motors were investigated using the kinesin subfamily members found in Trypanosoma brucei. (nottingham.ac.uk)
  • Our chapter in the kinesin superfamily handbook describes the largest subfamily, kinesin-3, a group of motors recently shown to be superprocessive and working as cellular long-distance transporters. (mechanochemistry.org)
  • The microscopy results showed fragmented centrosomes, multipolar mitotic spindles and errors in chromosome number following exposure to single walled carbon nanotube s (SWCNT). (cdc.gov)
  • These data support a model in which Tum/RacGAP, via its interaction with Pbl, provides a critical link between the anaphase microtubule spindle and cytokinetic furrow formation in Drosophila cells. (biologists.com)
  • The onset of anaphase is triggered by activation of the anaphase promoting complex/cyclosome (APC/C), following silencing of the spindle assembly checkpoint (SAC). (warwick.ac.uk)
  • A confocal Z-stack from a transgenic Drosophila expressing the kinesin-5 motor KLP61F-GFP embryo during prometaphase phase 1. (ucsd.edu)
  • This image is original data contributing to Fig. 1 "Prometaphase spindle dynamics in Drosophila embryos: steady-state and elongation phase" from Civelekoglu-Scholey et al. (ucsd.edu)
  • Motility is a fundamentally important property of most members of the kinesin superfamily, but a rare subset of kinesins are also able to alter microtubule dynamics. (nih.gov)
  • After multiple failed attempts to express and purify rsKif12, sequence analysis showed rsKif12 lacks nucleotide-binding motifs conserved across the kinesin superfamily. (nottingham.ac.uk)
  • The Kinesin-3 Family: Long-Distance Transporters in: The Kinesin Superfamily Handbook: Transporter, Creator, Destroyer, ed. (mechanochemistry.org)
  • As a microtubule (MT) cross-linking enzyme, KSP plays a critical role in mitotic spindle pole separation, and its inhibition results in the formation of monoaster spindles which is thought to lead to mitotic catastrophe and apoptosis (Fig. 1). (cytoskeleton.com)
  • The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. (strath.ac.uk)
  • Crystal Structure of the Mitotic Kinesin Eg5 in Complex with Mg-ADP. (expasy.org)
  • GSK-923295, is a small-molecule inhibitor of the mitotic kinesin centromere-associated protein E, (CENP-E). (adooq.com)
  • K 858 is a selective ATP-uncompetitive mitotic kinesin Eg5 inhibitor with IC50 value of 1.3 uM. (adooq.com)
  • Kif15-IN-2 is an inhibitor of the mitotic kinesin Kif15, and is used for the research of cellular proliferative diseases. (adooq.com)
  • Bod1 depletion does not affect the activity or localization of Aurora B but does cause mislocalization of the microtubule depolymerase mitotic centromere- associated kinesin and prevents its efficient phosphorylation by Aurora B. Therefore, Bod1 is a novel kinetochore protein that is required for the detection or resolution of syntelic attachments in mitotic spindles. (rupress.org)
  • Defects in spindle assembly or changes in spindle dynamics are associated with diseases, such as cancer or developmental disorders. (divide-eunetwork.org)
  • We identified the second kinesin-14 family protein Klp2 and microtubule dynamics as factors necessary for proper meiotic spindle assembly. (divide-eunetwork.org)
  • The report scope of Kinesin Spindle Protein market covers the in-depth analysis, along with an overview of market dynamics such as driver, restraints that are expected to impact the market growth. (prbulletin.com)
  • Cytoskeletal dynamics and spindle assembly during cell division. (irb.hr)
  • The stress-induced spindle pole convergence was also accompanied by poleward accumulation of the MT nucleator γ-tubulin. (figshare.com)
  • Involved in mitotic metaphase plate congression and mitotic spindle assembly. (nih.gov)
  • Using mutant and RNAi analysis, we show that the microtubule-bundling protein SPD-1/MAP-65 and BMK-1/kinesin-5 act as a brake opposing the force generated by the spindle midzone. (ens-lyon.fr)
  • This promotes relocalisation of Aurora B kinase, and other components of the chromosome passenger complex (CPC), from centromeres to the spindle midzone. (warwick.ac.uk)
  • We show that, even though mitotic and meiotic spindles underwent the typical three phases of spindle elongation, they have distinct features. (divide-eunetwork.org)
  • Here, we compared mitotic and meiotic spindles in fission yeast. (divide-eunetwork.org)
  • This work defines the differences between mitotic and meiotic spindles in fission yeast Schizosaccharomyces pombe, and provides prospect for future comparative studies.This article has an associated First Person interview with the first author of the paper. (divide-eunetwork.org)
  • In fission yeast this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6). (warwick.ac.uk)
  • ARRY-520 (Filanesib) is a synthetic kinesin spindle protein (KSP) inhibitor (IC50: 6 nM). (immunoportal.com)
  • KSP inhibitor ARRY-520 specifically inhibits KSP (kinesin-5 or Eg5) with potential antineoplastic activity. (adooq.com)
  • AZ 3146 is a potent and selective monopolar spindle 1 (Mps1) kinase inhibitor (IC50 = 35 nM). (adooq.com)
  • ARRY-520 R enantiomer is the R form of ARRY-520, which is a synthetic, small molecule kinesin spindle protein (KSP) inhibitor with IC50 of 6 nM. (adooq.com)
  • Dimethylenastron is an inhibitor of mitotic motor kinesin Eg5 with IC50 value of 200 nM. (adooq.com)
  • EMD534085 is a kinesin inhibitor currently in clinical development. (adooq.com)
  • Eg5 Inhibitor V, trans-24 is a potent and specific kinesin Eg5 inhibitor with an IC50 of 0.65 μM, and can be used in the research of cancer. (adooq.com)
  • BOS-172722 is an inhibitor of monopolar spindle 1 (MPS1) checkpoint with an IC50 of 2 nM. (adooq.com)
  • Litronesib is a selective, allosteric inhibitor of kinesin Eg5. (adooq.com)
  • BAY 1217389 is a potent, and selective inhibitor of the monopolar spindle 1 (MPS1) kinase with an IC50 value less than 10 nM. (adooq.com)
  • CCT251455 is a potent and selective mitotic kinase monopolar spindle 1 (MPS1) inhibitor with an IC50 of 3 nM. (adooq.com)
  • This motor protein is required for establishing the bipolar spindle. (biolegend.com)
  • My lab focuses on the mechanisms that generate specific microtubule arrays in polarised cells, the dynamic interactions of microtubule tips with intracellular structures and the cell cortex to control cell shape changes and the transport along microtubule arrays mediated by dynein and kinesins. (mechanochemistry.org)
  • We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. (biomedcentral.com)
  • Previous evidence points to numerous components of the spindle assembly checkpoint and mitotic regulation playing a major role in several cancers [ 11 , 12 ]. (biomedcentral.com)
  • Lastly, through gene expression profiling we have demonstrated disruption of the spindle assembly checkpoint in the paclitaxel resistant cell lines, indicating a potential therapeutic pathway. (biomedcentral.com)
  • Our results demonstrate disruption of the mitotic spindle by nanotube s and give further evidence of the mechanism responsible for the disruption of cell division. (cdc.gov)
  • Our results are the first to tubes (SWCNT) suggest the potential to interact report disruption of the mitotic spindle by with critical biological structures. (cdc.gov)
  • Small interfering RNA depletion of Bod1 in HeLa cells produces elongated mitotic spindles with severe biorientation defects. (rupress.org)
  • Kinesin-16s are found solely in organisms that build cilia/flagella, whilst Kinesin-13s are only absent in organisms that do not build cilia. (nottingham.ac.uk)
  • Kinesin-14 motor protein KIFC1 participates in DNA synthesis and chromatin maintenance. (nih.gov)
  • Kinesin Family Member C1 (KIFC1) Accelerates Proliferation and Invasion of Endometrial Cancer Cells Through Modulating the PI3K/AKT Signaling Pathway. (nih.gov)
  • Proper spindle function requires correct interplay between microtubule motors and non-motor proteins. (divide-eunetwork.org)
  • 2010) Prometaphase spindle maintenance by an antagonistic motor-dependent force balance made robust by a disassembling lamin-B envelope, J. Cell Biol. (ucsd.edu)
  • This protein is a catalytic kinesin motor with coiled-coil and Smc domains. (biolegend.com)
  • In this study, we focus on how two kinesins, the most common class of motor protein, bind to both their cargo and to MTs. (unm.edu)
  • KOP61-F is required to prevent prometaphase spindle collapse driven by the kinesin-14 Ncd. (ucsd.edu)
  • In Oct 2014, I became a Wellcome Investigator, and have used this opportunity to focus the lab more tightly around its core long-term interest of kinesin-microtubule interaction mechanisms. (warwick.ac.uk)
  • In this paper, we set out to identify the cytoskeletal ultrastructure in C. elegans mitotic spindles that underlies this function, and how this ultrastructure is generated, using a combination of large-scale electron tomography, light microscopy and mathematical modelling. (nature.com)
  • My lab focuses on the force generating mechanisms of kinesins and their microtubule tracks. (warwick.ac.uk)
  • In 2005, after a long period of development, Nick Carter and I published single molecule optical trapping experiments showing that kinesin-1 can be driven to walk backwards (doi: 10.1038/nature03528). (warwick.ac.uk)
  • The role of microtubule pivoting in formation of complex structures such as microtubule bundles and mitotic spindles. (irb.hr)
  • The larger multi-walled carbon nanotube s (MWCNT) primarily induced mitotic spindles with one mitotic spindle pole. (cdc.gov)