• Treatment of HeLa cells with paclitaxel induces phosphorylation of Aurora A at Thr288 while treatment with hydroxyurea ablates phosphorylation. (cellsignal.com)
  • Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis. (uchicago.edu)
  • GR phosphorylation by an Aurora kinase-dependent pathway provides the mechanism explaining the tight coupling GSK1904529A of ligand-independent GR phosphorylation to cell cycle phase because the maximal activity of these kinases occurs in mitosis. (ap26113.com)
  • TRIM69 redistributes MST2 to the perinuclear cytoskeleton, promotes its association with Polo-like kinase 1 (PLK1) and stimulates MST2 phosphorylation at S15 (a known PLK1 phosphorylation site that is critical for centrosome disjunction). (bvsalud.org)
  • At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. (imperial.ac.uk)
  • BTK, a TEC-family tyrosine kinase activated by the B-cell antigen receptor, contains a variety of regulatory domains and it is subject to complex regulation by membrane phospholipids, protein ligands, phosphorylation, and dimerization. (elifesciences.org)
  • We herein demonstrated that CADM1 interacts with Hippo pathway core kinases and enhances the phosphorylation of YAP1, and also that the membranous co-expression of CADM1 and LATS2 predicts a favorable prognosis in lung adenocarcinoma. (cancerindex.org)
  • In addition, PIP2 binds to polo-like kinase (PLK1) and reduces PLK1-mediated phosphorylation of MCAK. (biomedcentral.com)
  • In Drosophila phosphorylation of histone H3S10 in euchromatic chromatin regions by the JIL-1 tandem kinase has been implicated in counteracting heterochromatization and gene silencing. (silverchair.com)
  • This effect was absent when a `kinase dead' LacI-JIL-1 construct without histone H3S10 phosphorylation activity was expressed. (silverchair.com)
  • Instead, the `kinase dead' construct had a dominant-negative effect, leading to a disruption of chromatin structure that was associated with a global repression of histone H3S10 phosphorylation levels. (silverchair.com)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • Iain Cheeseman has been fascinated by the kinetochore since his days as a graduate student with David Drubin and Georjana Barnes at the University of California, Berkeley, where he identified a subgroup of kinetochore proteins called the Dam1 complex that links yeast chromosomes to the mitotic spindle ( 1 - 3 ). (rupress.org)
  • During mitosis, cohesion between sisters is maintained as chromosomes condense, attach to the mitotic spindle in a bipolar orientation, and congress to the metaphase plate. (silverchair.com)
  • Aurora-B, which is a member of the Chromosome Passenger Complex (CPC), is a key mitotic kinase and plays an important role in ensuring high fidelity mitosis by phosphorylating numerous substrates in the mitotic spindle. (virginia.edu)
  • Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • We identify Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69. (bvsalud.org)
  • The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. (cancerindex.org)
  • These kinases play a role in the formation of spindles, separation of chromosomes, as well as cytokinesis. (wikipedia.org)
  • Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. (oncotarget.com)
  • Plk1, the most thoroughly characterized member among the mammalian Plks, has multiple important roles in mitosis and cytokinesis, such as centrosome maturation, bipolar spindle formation, kinetochore-microtubule dynamics, activation of the anaphase promoting complex, chromosome segregation and execution of cytokinesis [ 3 , 4 , 13 ]. (oncotarget.com)
  • Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. (uchicago.edu)
  • Aurora B kinase promotes cytokinesis by inducing centralspindlin oligomers that associate with the plasma membrane. (uchicago.edu)
  • Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. (uchicago.edu)
  • Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation. (uchicago.edu)
  • It mediates proper CHROMOSOME SEGREGATION and contractile ring function during CYTOKINESIS. (lookformedical.com)
  • AZD6244 In relaxation from the cells, cleavage furrow formation was started but cytokinesis was soon aborted leading to fusion of two daughter cells into one polyploid cell (Figs. 4A, B). These results indicate that eupatorin impairs normal SAC signaling and suppresses normal cytokinesis when put on otherwise unperturbed mitotic cells, which fits using the phenotype caused by Aurora B kinase inhibitors. (mirnamimics.com)
  • The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
  • p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
  • Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
  • Since the discovery of Polo kinase in Drosophila in 1988 [ 1 ], the Polo-like kinase (Plk) family has been attracting enormous attention, both in academia and in pharmaceutical industry. (oncotarget.com)
  • The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous Chromosomes during meiosis. (uchicago.edu)
  • The resulting recombinase-coated ssDNA filaments can invade the homologous chromosome dsDNA, searching for a complementary sequence (chromosome pairing), which will foster genetic material exchange. (nature.com)
  • Prior to the first meiotic division, homologous chromosomes pair, synapse, and recombine to ensure their proper disjunction at anaphase I. Additionally, telomeres tethered at the nuclear envelope cluster in the bouquet configuration where they are subjected to dramatic pulling forces acting from outside of the nucleus. (biorxiv.org)
  • Taken together, our findings define a new OxPhos-DLBCL-specific pathogenetic loop involving SIRT1 and HSP90α that regulates chromosome dynamics during mitosis and may be exploited therapeutically. (bvsalud.org)
  • Apart from regulating kinetochore-microtubule attachment Aurora-B also regulates the assembly of the outer kinetochore during mitosis. (virginia.edu)
  • CSC-1: a subunit of the Aurora B kinase complex that binds to the survivin-like protein BIR-1 and the incenp-like protein ICP-1. (uchicago.edu)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
  • The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (imperial.ac.uk)
  • The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. (cancerindex.org)
  • These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)
  • They significantly increase chromosome instability and aneuploidy in a subset of hepatocellular carcinoma, resulting in growth inhibition. (carislifesciences.com)
  • Stringent control of centrosome duplication and separation is important for preventing chromosome instability. (bvsalud.org)
  • Errors in segregation of chromosomes can lead to genomic instability that underlies multiple developmental diseases and cancer. (virginia.edu)
  • The relationship between lysate protein concentration from paclitaxel-treated and hydroxyurea-treated HeLa cells and the absorbance at 450 nm using the PathScan ® RP Phospho-Aurora A (Thr288) Sandwich ELISA Kit #41333 is shown in the upper figure. (cellsignal.com)
  • The rapid protocol (RP) PathScan ® RP Phospho-Aurora A (Thr288) Sandwich ELISA Kit is a solid phase sandwich enzyme-linked immunosorbent assay (ELISA) that detects endogenous levels of Aurora A protein phosphorylated at Thr288 in a reduced assay time of 1.5 hours. (cellsignal.com)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
  • But a lot of the data that we found were consistent with a second role, directing chromosome segregation in a way that you wouldn't see for a purely microtubule-binding protein. (rupress.org)
  • GPCRKs are a family of protein kinases within the AGC (protein kinase A, protein kinase G, protein kinase C) group of kinases. (agckinases.com)
  • This gene targets the cyclin-dependent kinase inhibitor, p21, and causes cell differentiation, cell cycle arrest in G1, and ultimately apoptosis. (wikipedia.org)
  • By analysing tum/RacGAP50C mutant Drosophila embryos we show that cells lacking Tum do not form furrows and fail to localise the key cytokinetic components Pebble (a RhoGEF), Aurora B kinase, Diaphanous, Pav-KLP and Anillin. (biologists.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • The multi-subunit shelterin complexes bind along mammalian telomeres, shielding the natural chromosome ends from engaging the DNA damage signaling and repair machinery [ 1 ]. (prolekarniky.cz)
  • GSK1904529A Aurora A is found at centrosomes in early mitosis and controls centrosome maturation centriole separation and chromosome alignment (33) whereas accurate targeting of Aurora B to the chromosomes and then to the spindle midzone and midbody is essential for maintaining microtubule/kinetochore attachments and therefore faithful chromosomal segregation (34). (ap26113.com)
  • Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C Cdc20 , a key regulator of chromosome segregation in mitosis. (biomedcentral.com)
  • Without kinetochores, cells wouldn't get far in separating their chromosomes during mitosis. (rupress.org)
  • But kinetochores are much more than a simple link between DNA and microtubules-they coordinate chromosome and spindle dynamics, and are signaling centers that ensure the fidelity of chromosome inheritance. (rupress.org)
  • Cheeseman switched to C. elegans and human kinetochores for his postdoctoral studies, working with Arshad Desai at the Ludwig Institute for Cancer Research, in San Diego, CA. He purified a set of kinetochore proteins, called the KMN network, which forms the core microtubule-attachment site on metazoan chromosomes ( 4 , 5 ), and controls kinetochore assembly ( 6 ). (rupress.org)
  • Such dynamism is essential for assembling and positioning the bipolar spindle, searching for and docking with kinetochores, congressing and segregating chromosomes, and governing the spindle checkpoint [ 1 ]. (biomedcentral.com)
  • Centrosome separation and central spindle assembly act in redundant pathways that regulate microtubule density and trigger cleavage furrow formation. (uchicago.edu)
  • Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)
  • Eupatorin affects spindle formation, spindle integrity and centrosome separation To know why cells uncovered to eupatorin at G2 were postponed in mitosis we looked into when the flavonoid intervenes using the spindle dynamics, structure and/or MT polymerization. (mirnamimics.com)
  • The spindle assembly checkpoint promotes chromosome bi-orientation: A novel Mad1 role in chromosome alignment. (docksci.com)
  • Here we show that MLL1/KMT2A methylates Borealin K143 in the intrinsically disordered region essential for liquid-liquid phase separation of the chromosome passenger complex (CPC). (carislifesciences.com)
  • In Chapter 2, I will show that the liquid-liquid phase separation driven by the centromere-targeting region of the CPC is important for its inner-centromere localization and function and may underlie the mesoscale organization of the innercentromere. (virginia.edu)
  • Dao TP, Kolaitis R-M, Kim HJ, O'Donovan K, Martyniak B, Colicino E, Hehnly H, Taylor JP, Castañeda CA *. (2018) Ubiquitin modulates liquid-liquid phase separation of UBQLN2 via disruption of multivalent interactions. (syracuse.edu)
  • The TEC family kinase, BTK (Bruton's tyrosine kinase) is best known as the target of ibrutinib (IMBRUVICA®), the first-in-class covalent kinase active site inhibitor used to treat chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), and chronic graft-versus-host disease (cGVHD). (elifesciences.org)
  • Structures of the autoinhibited SRC family kinases were solved in 1997 revealing, for the first time, the compact arrangement of the SH3 and SH2 domains assembled onto the distal side of the catalytic kinase domain [ 4 ]. (elifesciences.org)
  • The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)
  • A . Schematic of the bouquet configuration of chromosomes during meiotic prophase I. The spatial arrangement of chromosomes with telomeres clustered and attached at the inner nuclear membrane is shown. (biorxiv.org)
  • In this study, we have identified TIN2-R282H, the most common DC-causing mutation in shelterin subunit TIN2, as a separation-of-function mutant which impairs telomerase recruitment to telomeres, but not chromosome end protection. (prolekarniky.cz)
  • Inhibiting MLL1 activity or mutating Borealin K143 to arginine perturbs CPC phase separation, reduces Aurora kinase B activity, and impairs the resolution of erroneous kinetochore-microtubule attachments and sister-chromatid cohesion. (carislifesciences.com)
  • Aurora-B activity at the kinetochore changes in response to the kinetochore-microtubule attachment status and this change is important for proper mitosis. (virginia.edu)
  • Securin degradation then unleashes separase to promote sister-chromatid separation. (biomedcentral.com)
  • Cheeseman began his own laboratory at the Whitehead Institute and the Biology Department at MIT in Cambridge, MA, in 2007 and recently characterized another kinetochore subcomplex that helps chromosomes move during anaphase by clinging on to depolymerizing spindle fibers ( 7 ). (rupress.org)
  • Cheeseman believes that the kinetochore parts list is nearing completion, and he is excited to begin understanding how they all combine to direct chromosome segregation. (rupress.org)
  • The TEC kinases are the second largest sub-family of non-receptor tyrosine kinases in the human genome after the SRC family [ 1 - 3 ]. (elifesciences.org)
  • B lymphocytes from a family with GR haploinsufficiency ( A ) were analyzed for chromosome complement by metaphase spread assay ( B ). Chromosome counts show counts for 150 cells from three impartial passages (p5-p8). (ap26113.com)
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
  • A previous screen of a human kinase and phosphatase shRNA library to select genes that mediate arsenite induction of spindle abnormalities resulted in the identification of phosphatidylinositol-5-phosphate 4-kinase type-2 gamma (PIP4KIIγ), a phosphatidylinositol 4,5-bisphosphate (PIP2)-synthesizing enzyme. (biomedcentral.com)
  • Finally, we evaluate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis. (nature.com)
  • Mitosis is usually a dynamic process controlled by the activity of multiple kinases with attendant modification of proteins facilitating rigid checkpoint control. (ap26113.com)
  • Rad51b c.92delT/c.92delT mice exhibited meiotic DNA repair defects due to RAD51 and HSF2BP/BMRE1 accumulation in the chromosome axes leading to a reduction in the number of crossovers. (nature.com)
  • Die beiden Structural Maintenance of Chromosomes (SMC)-Untereinheiten bilden zusammen mit einer Untereinheit aus der Familie der Kleisine eine dreigliedrige Ringstruktur aus, welche DNA-Stränge topologisch umschließen und dadurch intrachromosomale Verknüpfungen und Schlaufen stabilisieren kann. (uni-bayreuth.de)
  • Together, these data provide the first structural elucidation of full-length BTK and allow a deeper understanding of allosteric control over the BTK kinase domain during distinct stages of activation. (elifesciences.org)
  • The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. (imperial.ac.uk)
  • The problem with K562 cells, and many other cancer cell types, is an overabundance of Aurora kinases. (wikipedia.org)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • TRIM69-ablation in cancer cells leads to centrosome scattering and chromosome segregation defects. (bvsalud.org)
  • Moreover, the parS chromosomal context in non-replicative cells, combined with ParB depletion at cell division, critically contribute to the unique cell cycle-dependent organization of the centromere in this bacterium, highlighting new levels of complexity in chromosome segregation and cell cycle control. (bvsalud.org)
  • Mitosis is an important stage in the cell cycle when the duplicated chromosomes are segregated to the daughter cells. (virginia.edu)
  • This phenotype resembles the problem noticed in AZD2281 cells pretreated rich in power of nocodazole/vinblastine as individuals cells were resistant against eupatorin-caused forced mitotic exit even if Aurora B grew to become restricted. (mirnamimics.com)
  • Dao TP, Martyniak B, Canning AJ, Lei Y, Colicino EG, Cosgrove MS, Hehnly H, Castañeda CA*. (2019) ALS-linked mutations affect UBQLN2 oligomerization and phase separation in a position- and amino acid-dependent manner. (syracuse.edu)
  • Notably, mutations in the TPP1 OB-fold domain compromise telomerase-dependent telomere extension but not telomere end protection [ 18 , 21 ], indicating that TPP1 performs a role in telomerase regulation which is distinct from its contribution to chromosome end protection. (prolekarniky.cz)
  • The TEC and SRC kinases share the SH3-SH2-kinase domain arrangement (the 'Src module') ( Fig. 1a ). (elifesciences.org)
  • On the way to activation, disassembly of the SH3-SH2- kinase core opens a new autoinhibitory site on the kinase domain for PHTH domain binding that is ultimately released upon interaction of PHTH with PIP3. (elifesciences.org)
  • Membrane-induced dimerization activates BTK and we present here a crystal structure of an activation loop swapped BTK kinase domain dimer that likely represents the conformational state leading to trans-autophosphorylation. (elifesciences.org)
  • 5 ]. The three domains (SH3, SH2, kinase), the SH2-kinase linker, the activation loop and the active site are labeled. (elifesciences.org)