centrosome

Summary

Summary: The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).

Top Publications

  1. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
  2. pmc The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries
    Erich A Nigg
    Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Nat Cell Biol 13:1154-60. 2011
  3. pmc Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization
    V Mennella
    Department of Biochemistry and Biophysics and the Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94158, USA
    Nat Cell Biol 14:1159-68. 2012
  4. ncbi Centrioles, centrosomes, and cilia in health and disease
    Erich A Nigg
    Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Cell 139:663-78. 2009
  5. pmc Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways
    Liyun Sang
    Genentech Inc, South San Francisco, CA 94080, USA
    Cell 145:513-28. 2011
  6. pmc Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease
    Ramona A Hoh
    Department of Biology, Stanford University, Stanford, CA, USA
    PLoS ONE 7:e52166. 2012
  7. pmc Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods
    Lis Jakobsen
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    EMBO J 30:1520-35. 2011
  8. ncbi Microtubule nucleation by γ-tubulin complexes
    Justin M Kollman
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143, USA
    Nat Rev Mol Cell Biol 12:709-21. 2011
  9. pmc Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry
    Daniël Splinter
    Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands
    PLoS Biol 8:e1000350. 2010
  10. pmc SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice
    Xiaochang Zhang
    Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, China
    Neuron 64:173-87. 2009

Research Grants

  1. Identifying all Meckel-like ciliopathy genes by established total exome capture a
    Friedhelm Hildebrandt; Fiscal Year: 2010
  2. MECHANISMS OF INTESTINAL TUMORIGENESIS
    Vincent W Yang; Fiscal Year: 2013
  3. Targeting Mitotic Kinases Inhibitors for Cancer Therapy
    E Premkumar Reddy; Fiscal Year: 2013
  4. Centrosomin and Centrosomes in Cell Division
    Timothy L Megraw; Fiscal Year: 2012
  5. Molecular and cellular mechanism of Microcephaly
    Arnold Kriegstein; Fiscal Year: 2013
  6. Genetic Analysis of Mouse Nervous System Development
    Kathryn V Anderson; Fiscal Year: 2013
  7. GENETIC ANALYSIS OF BASAL BODY FUNCTION
    Susan K Dutcher; Fiscal Year: 2013
  8. Function of the chromosomal kinase haspin in mitosis
    JONATHAN M HIGGINS; Fiscal Year: 2010
  9. Developmental Regulation of the Cell Cycle in Drosophila
    LAURA ANNE LEE; Fiscal Year: 2013
  10. Role of ORCA in DNA replication
    Supriya Gangadharan Prasanth; Fiscal Year: 2013

Detail Information

Publications334 found, 100 shown here

  1. pmc A mechanism linking extra centrosomes to chromosomal instability
    Neil J Ganem
    Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 460:278-82. 2009
    ..To define the mechanism underlying this mitotic defect, we generated cells that differ only in their centrosome number...
  2. pmc The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries
    Erich A Nigg
    Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Nat Cell Biol 13:1154-60. 2011
    ..At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated ..
  3. pmc Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization
    V Mennella
    Department of Biochemistry and Biophysics and the Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94158, USA
    Nat Cell Biol 14:1159-68. 2012
    As the main microtubule-organizing centre in animal cells, the centrosome has a fundamental role in cell function. Surrounding the centrioles, the pericentriolar material (PCM) provides a dynamic platform for nucleating microtubules...
  4. ncbi Centrioles, centrosomes, and cilia in health and disease
    Erich A Nigg
    Biozentrum, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Cell 139:663-78. 2009
    ..Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in ..
  5. pmc Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways
    Liyun Sang
    Genentech Inc, South San Francisco, CA 94080, USA
    Cell 145:513-28. 2011
    ..Our study further illustrates the power of linking proteomic networks and human genetics to uncover critical disease pathways...
  6. pmc Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease
    Ramona A Hoh
    Department of Biology, Stanford University, Stanford, CA, USA
    PLoS ONE 7:e52166. 2012
    Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes...
  7. pmc Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods
    Lis Jakobsen
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    EMBO J 30:1520-35. 2011
    ..Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads to the further functional characterization of centrosomal proteins...
  8. ncbi Microtubule nucleation by γ-tubulin complexes
    Justin M Kollman
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143, USA
    Nat Rev Mol Cell Biol 12:709-21. 2011
    ..New experiments on γTuRC localization extend these insights, suggesting a direct link between its attachment at specific cellular sites and its activation...
  9. pmc Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry
    Daniël Splinter
    Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands
    PLoS Biol 8:e1000350. 2010
    ....
  10. pmc SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice
    Xiaochang Zhang
    Institute of Developmental Biology and Molecular Medicine, School of Life Science, Fudan University, Shanghai, China
    Neuron 64:173-87. 2009
    ..We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex...
  11. pmc The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin
    A K Gillingham
    MRC Laboratory of Molecular Biology, Cambridge, UK
    EMBO Rep 1:524-9. 2000
    ..When isolated from transfected cells the C-terminal domain of AKAP450 was associated with calmodulin, suggesting that this protein could contribute to centrosome assembly.
  12. pmc Mechanisms of chromosomal instability
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 20:R285-95. 2010
    ..review the mechanisms underlying CIN, which include defects in chromosome cohesion, mitotic checkpoint function, centrosome copy number, kinetochore-microtubule attachment dynamics, and cell-cycle regulation...
  13. pmc CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex
    Ka Wing Fong
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    Mol Biol Cell 19:115-25. 2008
    Microtubule nucleation and organization by the centrosome require gamma-tubulin, a protein that exists in a macromolecular complex called the gamma-tubulin ring complex (gammaTuRC)...
  14. pmc A clinical overview of centrosome amplification in human cancers
    Jason Yongsheng Chan
    Ministry of Health Holdings, Singapore
    Int J Biol Sci 7:1122-44. 2011
    The turn of the 21st century had witnessed a surge of interest in the centrosome and its causal relation to human cancer development - a postulate that has existed for almost a century...
  15. ncbi Microtubule-organizing centres: a re-evaluation
    Jens Lüders
    Department of Biological Sciences, Stanford University, CA 94305, USA
    Nat Rev Mol Cell Biol 8:161-7. 2007
    ..These findings suggest that the spatio-temporal control of microtubule nucleation is more complex than previously thought, leading us to a re-evaluation of the concept of the microtubule-organizing center...
  16. pmc Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections
    David Razafsky
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 186:461-72. 2009
    ..Moreover, we discuss the function of these complexes in nuclear, centrosomal, and chromosome dynamics, and their connection to human disease...
  17. ncbi The C. elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus
    Christian J Malone
    Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA
    Cell 115:825-36. 2003
    The centrosome and nucleus are intimately associated in most animal cells, yet the significance of this interaction is unknown...
  18. ncbi Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells
    Elena Rebollo
    Cell Division Group, Institute for Research in Biomedicine, Parc Científic Barcelona, C Josep Samitier 1 5, 08028 Barcelona, Spain
    Dev Cell 12:467-74. 2007
    ..Upon division, the apical centrosome remains in the stem cell, while the other goes into the differentiating daughter...
  19. pmc Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome
    Christopher J Westlake
    Genentech, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 108:2759-64. 2011
    ..assembly is initiated by the relocalization of Rabin8 to Rab11-positive vesicles that are transported to the centrosome. After ciliogenesis, Rab8 ciliary transport is strongly reduced, and this reduction appears to be associated ..
  20. ncbi Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe
    Diane R Wonsey
    Department of Discovery Medicine, Wyeth Research, Cambridge, Massachusetts, USA
    Cancer Res 65:5181-9. 2005
    ..These findings indicate that FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting FoxM1 represents a therapeutic strategy to target breast cancer...
  21. ncbi Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells
    Toru Hirota
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Japan
    Cell 114:585-98. 2003
    ..Depletion of Ajuba prevented activation of Aurora-A at centrosomes in late G2 phase and inhibited mitotic entry. Overall, our data suggest that Ajuba is an essential activator of Aurora-A in mitotic commitment...
  22. ncbi Mechanisms of centrosome separation and bipolar spindle assembly
    Marvin E Tanenbaum
    Department of Medical Oncology, University Medical Center, CG Utrecht, The Netherlands
    Dev Cell 19:797-806. 2010
    ..Here, we discuss different pathways that promote initial centrosome separation and bipolar spindle assembly.
  23. ncbi Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes
    Melina Schuh
    Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Cell 130:484-98. 2007
    ..Here, we analyze centrosome-independent spindle assembly by quantitative high-resolution confocal imaging in live maturing mouse oocytes...
  24. pmc EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms
    Jacob M Schrøder
    Department of Biology, University of Copenhagen, Universitetsparken 13, DK 2100 Copenhagen, Denmark
    J Cell Sci 124:2539-51. 2011
    ..microscopy and live imaging showed that cells lacking EB1 or EB3 are defective in MT minus-end anchoring at the centrosome and/or basal body, and possess abnormally short cilia stumps surrounded by vesicles...
  25. pmc Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis
    Kazuhisa Kinoshita
    Max Planck Institute of Molecular Cell Biology and Genetics MPI CBG, 01307 Dresden, Germany
    J Cell Biol 170:1047-55. 2005
    ..of microtubule growth, but little is known about how the number and stability of microtubules emanating from a centrosome are controlled during the cell cycle...
  26. pmc Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors
    Sofia B Lizarraga
    Division of Genetics and the Manton Center for Orphan Disease Research, Children s Hospital Boston, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Development 137:1907-17. 2010
    ..Our findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation...
  27. ncbi Structures of SAS-6 suggest its organization in centrioles
    Mark van Breugel
    Medical Research Council Laboratory of Molecular Biology MRC LMB, Hills Road, Cambridge, UK
    Science 331:1196-9. 2011
    ..Thus, these interactions are probably essential to the structural organization of cartwheel centers...
  28. pmc Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome
    Onur Cizmecioglu
    Cell Cycle Control and Carcinogenesis, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    J Cell Biol 191:731-9. 2010
    ..the Polo-like kinase Plk4/Sak as a crucial regulator of centriole biogenesis, but the mechanisms governing centrosome duplication are incompletely understood...
  29. ncbi The cellular geography of aurora kinases
    Mar Carmena
    Wellcome Trust Centre for Cell Biology, Institute for Cell and Molecular Biology, Kings Buildings, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, Scotland, UK
    Nat Rev Mol Cell Biol 4:842-54. 2003
  30. pmc A genome-wide RNAi screen to dissect centriole duplication and centrosome maturation in Drosophila
    Jeroen Dobbelaere
    The Gurdon Institute, Cambridge, United Kingdom
    PLoS Biol 6:e224. 2008
    ..We analysed 92% of the Drosophila genome (13,059 genes) and identified 32 genes involved in centrosome function...
  31. pmc Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells
    Yutaka Kondo
    Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan
    PLoS ONE 3:e2037. 2008
    ..Cancer cells are characterized by prominent epigenetic dysregulation, including histone modifications. However, the functional roles of the histone methyltransferases (HMT) in cancer remain unclear...
  32. pmc Proper recruitment of gamma-tubulin and D-TACC/Msps to embryonic Drosophila centrosomes requires Centrosomin Motif 1
    Jiuli Zhang
    Department of Pharmacology, The Cecil and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9051, USA
    Mol Biol Cell 18:4037-49. 2007
    ..Although the individual binding steps in centrosome maturation are largely unknown, Centrosomin (Cnn) is an essential mitotic centrosome component required for ..
  33. pmc Centrosome amplification drives chromosomal instability in breast tumor development
    Wilma L Lingle
    Division of Experimental Pathology, Tumor Biology Program, Mayo Clinic, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 99:1978-83. 2002
    ..In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human ..
  34. pmc A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons
    Albert H Kim
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 136:322-36. 2009
    ..Remarkably, Cdc20 is enriched at the centrosome in neurons, and the centrosomal localization is critical for Cdc20-dependent dendrite development...
  35. pmc Regulating the transition from centriole to basal body
    Tetsuo Kobayashi
    Department of Pathology, School of Medicine, New York University Cancer Institute, New York, NY 10016, USA
    J Cell Biol 193:435-44. 2011
    ..Emerging studies also provide insights into how defects in the balance between centrosome and cilia function could promote ciliopathies and cancer.
  36. pmc PLK1 phosphorylation of pericentrin initiates centrosome maturation at the onset of mitosis
    Kwanwoo Lee
    Department of Biological Sciences, Seoul National University, Seoul 151 747, South Korea
    J Cell Biol 195:1093-101. 2011
    The microtubule-organizing activity of the centrosome oscillates during the cell cycle, reaching its highest level at mitosis...
  37. ncbi Asterless is a scaffold for the onset of centriole assembly
    Nikola S Dzhindzhev
    Cancer Research UK Cell Cycle Genetics Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK
    Nature 467:714-8. 2010
    Centrioles are found in the centrosome core and, as basal bodies, at the base of cilia and flagella...
  38. pmc SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation
    Vincenzo D'Angiolella
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA
    Nature 466:138-42. 2010
    ..Starting from an unbiased screen, we identified CP110, a protein that is essential for centrosome duplication, as an interactor and substrate of Cyclin F...
  39. ncbi Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome
    Youmna Kfoury
    Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
    Blood 117:190-9. 2011
    ..Tax localizes to Tax nuclear bodies and to the centrosome and is subjected to ubiquitylation and small ubiquitin-like modifier (SUMO)ylation, which are both necessary for ..
  40. pmc Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network
    Andrey Efimov
    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Dev Cell 12:917-30. 2007
    ..It is generally assumed that most if not all microtubules in vertebrate somatic cells are formed by the centrosome. Here we demonstrate that a large number of microtubules in untreated human cells originate from the Golgi ..
  41. ncbi Cep97 and CP110 suppress a cilia assembly program
    Alexander Spektor
    Department of Pathology and NYU Cancer Institute, New York University School of Medicine, Smilow Research Center, 522 First Avenue, New York, NY 10016, USA
    Cell 130:678-90. 2007
    Mammalian centrioles play a dynamic role in centrosome function, but they also have the capacity to nucleate the assembly of cilia. Although controls must exist to specify these different fates, the key regulators remain largely undefined...
  42. ncbi The Aurora kinase family in cell division and cancer
    Gerben Vader
    Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center Utrecht, Stratenum 2 125, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochim Biophys Acta 1786:60-72. 2008
    ....
  43. ncbi Proteomic characterization of the human centrosome by protein correlation profiling
    Jens S Andersen
    Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK 5230 Odense M, Denmark
    Nature 426:570-4. 2003
    The centrosome is the major microtubule-organizing centre of animal cells and through its influence on the cytoskeleton is involved in cell shape, polarity and motility...
  44. ncbi Kif15 cooperates with eg5 to promote bipolar spindle assembly
    Marvin E Tanenbaum
    Department of Medical Oncology and Cancer Genomics Centre, University Medical Center Utrecht, The Netherlands
    Curr Biol 19:1703-11. 2009
    ..the highly conserved microtubule motor Eg5 (kinesin-5), which can slide antiparallel microtubules apart to drive centrosome separation...
  45. pmc The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles
    Giulia Guarguaglini
    Department of Cell Biology, Max Planck Institute for Biochemistry, D 82152, Martinsried, Germany
    Mol Biol Cell 16:1095-107. 2005
    ..We show that Cep170 labeling can be used to discriminate bona fide centriole overduplication from centriole amplification that results from aborted cell division...
  46. ncbi Centrioles regulate centrosome size by controlling the rate of Cnn incorporation into the PCM
    Paul T Conduit
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Curr Biol 20:2178-86. 2010
    ..b>Centrosome size is tightly regulated during the cell cycle, and it has recently been shown that the two centrosomes in ..
  47. pmc Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo
    P GONCZY
    European Molecular Biology Laboratory, Heidelberg, D 69117 Germany
    J Cell Biol 147:135-50. 1999
    ..interference contrast microscopy and indirect immunofluorescence revealed that pronuclear migration and centrosome separation failed in one cell stage dhc-1 (RNAi) embryos...
  48. ncbi Centrosome localization determines neuronal polarity
    Froylan Calderon de Anda
    Cavalieri Ottolenghi Scientific Institute, Universita degli Studi di Torino, 10043 Orbassano, Torino, Italy
    Nature 436:704-8. 2005
    ..polymerization and membrane transport precedes first neurite formation, (2) neurons with more than one centrosome sprout more than one axon and (3) suppression of centrosome-mediated functions precludes polarization...
  49. ncbi The centrosome in cells and organisms
    Michel Bornens
    UMR144 du Centre Nationale de la Recherche Scientifique, Institut Curie, 26 Rue d Ulm, Paris Cedex 05, France
    Science 335:422-6. 2012
    The centrosome acts as the main microtubule-nucleating organelle in animal cells and plays a critical role in mitotic spindle orientation and in genome stability...
  50. pmc Centrosomes and cilia in human disease
    Monica Bettencourt-Dias
    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Trends Genet 27:307-15. 2011
    ..The centrosome is the major microtubule organiser in animal cells, participating in a variety of processes, from cell ..
  51. pmc Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans
    E Hannak
    Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
    J Cell Biol 155:1109-16. 2001
    ..Here, we use RNA-mediated interference (RNAi) to examine the role of the aurora-A kinase, AIR-1, during centrosome maturation in Caenorhabditis elegans...
  52. ncbi STIL is required for centriole duplication in human cells
    Julia Vulprecht
    Clinical Cooperation Unit Molecular Hematology Oncology, German Cancer Research Center DKFZ and Dept of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany
    J Cell Sci 125:1353-62. 2012
    ..These findings demonstrate that STIL is an essential component of the centriole replication machinery in mammalian cells...
  53. pmc Cdk5rap2 exposes the centrosomal root of microcephaly syndromes
    Timothy L Megraw
    Department of Biomedical Sciences, Florida State University, College of Medicine, Tallahassee, USA
    Trends Cell Biol 21:470-80. 2011
    ..We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain...
  54. pmc Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly
    Arun Kumar
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India
    Am J Hum Genet 84:286-90. 2009
    ..There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain.
  55. ncbi Prediction of midbody, centrosome and kinetochore proteins based on gene ontology information
    Wei Chen
    Department of Physics, School of Basic Medical Sciences, North China Coal Medical University, Tangshan 063000, China
    Biochem Biophys Res Commun 401:382-4. 2010
    ..process of cell division, a great deal of proteins is assembled into three distinct organelles, namely midbody, centrosome and kinetochore...
  56. pmc USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110
    Ji Li
    Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, 522 1st Avenue, New York, New York 10016, USA
    Nature 495:255-9. 2013
    b>Centrosome duplication is critical for cell division, and genome instability can result if duplication is not restricted to a single round per cell cycle...
  57. pmc USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis
    Ying Zhang
    Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Invest 122:4362-74. 2012
    ..USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry...
  58. pmc Dynamic association of proteasomal machinery with the centrosome
    W C Wigley
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
    J Cell Biol 145:481-90. 1999
    ..The centrosome-associated structure enlarges in response to inhibition of proteasome activity and the level of misfolded ..
  59. ncbi PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody
    Antonia P Sagona
    Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N 0310 Oslo, Norway
    Nat Cell Biol 12:362-71. 2010
    ..Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A...
  60. pmc The elegans of spindle assembly
    Thomas Müller-Reichert
    Medical Theoretical Center MTZ, TU Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
    Cell Mol Life Sci 67:2195-213. 2010
    ..resulting maternal DNA then unites with the paternal DNA to form a zygotic diploid complement, around which a centrosome-based mitotic spindle forms. The early C...
  61. pmc Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia
    E Scott Seeley
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Cancer Res 69:422-30. 2009
    ..Thus, arrested ciliogenesis is a cardinal feature of PDAC and its precursor PanIN lesions, does not require ongoing proliferation, and could potentially be targeted pharmacologically...
  62. ncbi Generation of noncentrosomal microtubule arrays
    Francesca Bartolini
    Department of Anatomy, Columbia University, New York, NY 10032, USA
    J Cell Sci 119:4155-63. 2006
    In most proliferating and migrating animal cells, the centrosome is the main site for microtubule (MT) nucleation and anchoring, leading to the formation of radial MT arrays in which MT minus ends are anchored at the centrosomes and plus ..
  63. ncbi Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication
    Wei Wang
    Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Nat Cell Biol 7:823-30. 2005
    b>Centrosome duplication is tightly controlled during faithful cell division, and unnecessary reduplication can lead to supernumerary centrosomes and multipolar spindles that are associated with most human cancer cells...
  64. pmc A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase
    Stéphanie Bolhy
    Cell Biology Program, Institut Jacques Monod, UMR 7592 Centre National de la Recherche Scientifique Université Paris Diderot, 75205 Paris Cedex 13, France
    J Cell Biol 192:855-71. 2011
    ..We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously ..
  65. ncbi Centrosomes, microtubules and neuronal development
    Marijn Kuijpers
    Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
    Mol Cell Neurosci 48:349-58. 2011
    ..The centrosome serves as the main cytoskeleton-organizing center in the cell and is the classical site of microtubule ..
  66. ncbi Axon extension occurs independently of centrosomal microtubule nucleation
    Michael Stiess
    Independent Junior Research Group Axonal Growth and Regeneration, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany
    Science 327:704-7. 2010
    ..Their dynamic polymerization is important for diverse cellular functions. The centrosome is the classical site of microtubule nucleation and is thought to be essential for axon growth and neuronal ..
  67. ncbi Centrosome function in cancer: guilty or innocent?
    Deborah Zyss
    Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK
    Trends Cell Biol 19:334-46. 2009
    The regulation of centrosome number and function underlies bipolar mitotic spindle formation and genetic integrity. Cancer cells both in culture and in situ exhibit a wide range of centrosome abnormalities...
  68. ncbi Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster
    Emmanuel Caussinus
    Cell Biology and Biophysics Program, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nat Genet 37:1125-9. 2005
    ..Six weeks after the first implantation, genome instability and centrosome alterations, two traits of malignant carcinomas, appeared in these tumors...
  69. pmc Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis
    Xuecai Ge
    Picower Institute for Learning and Memory, Department of Brain and Cognitive, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46, Room 4235A, Cambridge, MA 02139, USA
    Neuron 65:191-203. 2010
    b>Centrosome functions are important in multiple brain developmental processes. Proper functioning of the centrosome relies on assembly of protein components into the pericentriolar material...
  70. pmc Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance
    Supriya G Prasanth
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    EMBO J 23:2651-63. 2004
    ..These results implicate Orc2 protein in chromosome duplication, chromosome structure and centrosome copy number control, suggesting that it coordinates all stages of the chromosome inheritance cycle.
  71. ncbi Genomic instability in Gadd45a-deficient mice
    M C Hollander
    Gene Response Section, DBS, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    Nat Genet 23:176-84. 1999
    ..Genomic instability was exemplified by aneuploidy, chromosome aberrations, gene amplification and centrosome amplification, and was accompanied by abnormalities in mitosis, cytokinesis and growth control...
  72. ncbi Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis
    Megan Fabbro
    Queensland Institute of Medical Research, P O Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia
    Dev Cell 9:477-88. 2005
    ..Here, we describe a human coiled-coil protein, Cep55 (centrosome protein 55 kDa), that localizes to the mother centriole during interphase...
  73. ncbi Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8
    Coralie Petit
    CNRS UPR9051, Hopital Saint Louis, Conventionné par l Université Paris 7, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
    J Cell Sci 116:3433-42. 2003
    ..Trafficking of Gag towards the centrosome requires a minimal 30 amino acid coiled-coil motif in the N-terminus of the molecule...
  74. ncbi Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication
    M Okuda
    Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Ohio 45267, USA
    Cell 103:127-40. 2000
    ..We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication...
  75. pmc Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells
    Patrick Meraldi
    Department of Cell Biology, Max Planck Institute for Biochemistry, D 82152 Martinsried, Germany
    EMBO J 21:483-92. 2002
    Aberrations in centrosome numbers have long been implicated in aneuploidy and tumorigenesis, but their origins are unknown. Here we have examined how overexpression of Aurora-A kinase causes centrosome amplification in cultured cells...
  76. pmc Pericentrin in cellular function and disease
    Benedicte Delaval
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Cell Biol 188:181-90. 2010
    Pericentrin is an integral component of the centrosome that serves as a multifunctional scaffold for anchoring numerous proteins and protein complexes...
  77. ncbi A kinesin-like motor inhibits microtubule dynamic instability
    Henrik Bringmann
    Cell Biology and Biophysics Programme, European Molecular Biology Laboratory, Meyerhofstrabetae 1, 69117 Heidelberg, Germany
    Science 303:1519-22. 2004
    ..The integration of the two properties, motility and inhibition of microtubule dynamics, in one molecule emphasizes the versatile properties of kinesin family members...
  78. ncbi Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division
    Akira Nakanishi
    Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, 3 10 6 Ariake, Koto ku, Tokyo 135 8550, Japan
    Biochem Biophys Res Commun 355:34-40. 2007
    ..These results thus implicate BRCA2 in the regulation of the centrosome cycle, and provide new insight into the aneuploid nature of many breast cancers.
  79. ncbi The role of nucleophosmin in centrosome duplication
    Masaru Okuda
    Laboratory of Veterinary Internal Medicine, Faculty of Agriculture, Yamaguchi University, Yoshida 1677 1, Yamaguchi, Japan, 753 8515
    Oncogene 21:6170-4. 2002
    ..NPM)/B23, a multifunctional protein, has recently been identified as one of the substrates of CDK2/cyclin E in centrosome duplication...
  80. ncbi Molecular mechanisms of centrosome and cytoskeleton anchorage at the nuclear envelope
    Maria Schneider
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK
    Cell Mol Life Sci 68:1593-610. 2011
    ..of nesprin-2/SUN-domain protein associations impairs cell polarization during wounding and dislodges the centrosome from the NE...
  81. ncbi The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Oncogene 23:4353-61. 2004
    ..Inhibition of Chk2 thus can sensitize proliferating cells to chemotherapy-induced apoptosis...
  82. pmc Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells
    Christopher Kasbek
    Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210 1292, USA
    Mol Biol Cell 18:4457-69. 2007
    ..cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication...
  83. pmc Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly
    Marvin E Tanenbaum
    Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
    EMBO J 27:3235-45. 2008
    ..As such, Eg5 can produce the necessary outward force within the spindle that drives centrosome separation and inhibition of this antiparallel sliding activity results in the formation of monopolar spindles...
  84. ncbi Chromosomal instability in osteosarcoma and its association with centrosome abnormalities
    K Al-Romaih
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Cancer Genet Cytogenet 144:91-9. 2003
    ..We also investigated whether there was an association between TP53 mutation and centrosome aberrations in the generation of chromosomal aneuploidy in OS in four OS cell lines (HOS, SAOS2, U2OS, and MG63) ..
  85. pmc Hsp90 is a core centrosomal component and is required at different stages of the centrosome cycle in Drosophila and vertebrates
    B M Lange
    Cell Biology and Cell Biophysics Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    EMBO J 19:1252-62. 2000
    To determine the molecular composition of the centrosome of a higher eukaryote, we carried out a systematic nano-electrospray tandem or MALDI mass spectrometry analysis of the polypeptides present in highly enriched preparations of ..
  86. ncbi The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression
    Jun Chul Kim
    Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr, Burnaby BC, V5A 1S6, Canada
    Nat Genet 36:462-70. 2004
    ....
  87. ncbi Suppression of centrosome amplification after DNA damage depends on p27 accumulation
    Eiji Sugihara
    Nagahama Institute of Bio Science and Technology, Shiga, Japan
    Cancer Res 66:4020-9. 2006
    The centrosome plays a fundamental role in cell division, cell polarity, and cell cycle progression...
  88. pmc Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells
    Paul M Miller
    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Nat Cell Biol 11:1069-80. 2009
    ....
  89. pmc Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly
    Alberto Toso
    Institute of Biochemistry, ETH Zurich, CH 8093 Zurich, Switzerland
    J Cell Biol 184:365-72. 2009
    In animal somatic cells, bipolar spindle formation requires separation of the centrosome-based spindle poles...
  90. pmc Centrosomes split in the presence of impaired DNA integrity during mitosis
    Henderika M J Hut
    Department of Radiation and Stress Cell Biology, Faculty of Medical Sciences, University of Groningen, The Netherlands
    Mol Biol Cell 14:1993-2004. 2003
    ..This results in the formation of multipolar spindles with extra centrosome-like structures...
  91. pmc Plk1-dependent and -independent roles of an ODF2 splice variant, hCenexin1, at the centrosome of somatic cells
    Nak Kyun Soung
    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 16:539-50. 2009
    ..These findings provide a striking example of how a splice-generated C-terminal extension of a sperm tail-associating protein mediates unanticipated centrosomal events at distinct stages of the somatic cell cycle...
  92. pmc Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction
    Balca R Mardin
    Zentrum fur Molekulare Biologie der Universitat Heidelberg, DKFZ ZMBH Allianz, Im Neuenheimer Feld 282, 69117 Heidelberg, Germany
    Nat Cell Biol 12:1166-76. 2010
    ..This linker is disassembled at the onset of mitosis in a process known as centrosome disjunction, thereby facilitating centrosome separation and bipolar spindle formation...
  93. ncbi DISC1, PDE4B, and NDE1 at the centrosome and synapse
    Nicholas J Bradshaw
    Medical Genetics Section, Molecular Medicine Centre, Crewe Road, Edinburgh EH4 2XU, United Kingdom
    Biochem Biophys Res Commun 377:1091-6. 2008
    ..associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, ..
  94. pmc Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization
    Andrew B Fielding
    Department of Cancer Genetics, British Columbia Cancer Research Centre of the British Columbia Cancer Agency, Vancouver, BC, Canada
    J Cell Biol 180:681-9. 2008
    ..These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation...
  95. ncbi Mechanisms of asymmetric cell division: flies and worms pave the way
    PIERRE GONCZY
    Swiss Institute for Experimental Cancer Research ISREC, Swiss Federal Institute of Technology EPFL, School of Life Sciences, Lausanne, Switzerland
    Nat Rev Mol Cell Biol 9:355-66. 2008
    ..Lessons learned from these two model organisms also apply to cells that divide asymmetrically in other metazoans, such as self-renewing stem cells in mammals...
  96. pmc TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly
    Lynne Cassimeris
    Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA
    Mol Biol Cell 15:1580-90. 2004
    ..TOGp localized to centrosomes in the absence of MTs and depletion of TOGp resulted in centrosome fragmentation...
  97. ncbi Limiting amounts of centrosome material set centrosome size in C. elegans embryos
    Markus Decker
    Max Planck Institute for Cell Biology and Genetics, Dresden 01307 Germany
    Curr Biol 21:1259-67. 2011
    ..Embryonic cells must therefore possess simple and robust mechanisms that allow the size of many of their intracellular structures to rapidly scale with cell size...
  98. ncbi The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication
    Anja Puklowski
    Institute for Molecular Biology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Cell Biol 13:1004-9. 2011
    Deregulated centrosome duplication can result in genetic instability and contribute to tumorigenesis...
  99. pmc Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5
    M Teresa Bertran
    Cell Signalling Research Group, Molecular Medicine Program, Institute for Research in Biomedicine IRB Barcelona, Barcelona, Spain
    EMBO J 30:2634-47. 2011
    ..Furthermore, we show that Plk1 controls prophase centrosome separation through the activation of Nek9 and ultimately the phosphorylation of the mitotic kinesin Eg5 at ..
  100. pmc Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A
    Poonam R Molli
    Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA
    J Cell Biol 190:101-14. 2010
    ..Arp2/3 complex, in regulation of mitosis and demonstrate that its depletion inhibits Aurora A activation at the centrosome and impairs the ability of mammalian cells to enter mitosis...
  101. ncbi Homologous recombination proteins are associated with centrosomes and are required for mitotic stability
    Enrico Cappelli
    Medical Research Council, Radiation and Genome Stability Unit, Oxon OX11 0RD, UK
    Exp Cell Res 317:1203-13. 2011
    ..Cells deficient in XRCC2 also show disruption of the centrosome, a key component of the mitotic apparatus...

Research Grants66

  1. Identifying all Meckel-like ciliopathy genes by established total exome capture a
    Friedhelm Hildebrandt; Fiscal Year: 2010
    ..Identification of mutations in proteins of the primary cilia-centrosome complex (CCC) defined the disease group of "retinal-renal ciliopathies", the most frequent genetic cause of ..
  2. MECHANISMS OF INTESTINAL TUMORIGENESIS
    Vincent W Yang; Fiscal Year: 2013
    ..Lastly, ablation of KLF4 results in genetic instability including centrosome amplification, chromosome aberrations and aneuploidy...
  3. Targeting Mitotic Kinases Inhibitors for Cancer Therapy
    E Premkumar Reddy; Fiscal Year: 2013
    ..of 285 kinases revealed that this compound had a remarkable specificity towards Plk2/Snk, a kinase involved in centrosome duplication and mitotic progression...
  4. Centrosomin and Centrosomes in Cell Division
    Timothy L Megraw; Fiscal Year: 2012
    ..syndromes that affect brain and/or body size, yet an understanding of the connection between function at the centrosome and the causes of disease are unclear...
  5. Molecular and cellular mechanism of Microcephaly
    Arnold Kriegstein; Fiscal Year: 2013
    ..Five of eight MCPH genes localize to the centrosome during all or part of the cell cycle...
  6. Genetic Analysis of Mouse Nervous System Development
    Kathryn V Anderson; Fiscal Year: 2013
    ..Cilia are templated by centrosomes, and human genetic diseases that disrupt the centrosome cause microcephaly...
  7. GENETIC ANALYSIS OF BASAL BODY FUNCTION
    Susan K Dutcher; Fiscal Year: 2013
    ..The structure and composition of these organelles is conserved among organisms. The animal and algal centrosome consists of pericentriolar material and a pair of cylinders called centrioles or basal bodies...
  8. Function of the chromosomal kinase haspin in mitosis
    JONATHAN M HIGGINS; Fiscal Year: 2010
    ..We have also isolated candidate haspin-binding proteins that are consistent with haspin function at the centrosome and spindle...
  9. Developmental Regulation of the Cell Cycle in Drosophila
    LAURA ANNE LEE; Fiscal Year: 2013
    ..by promoting dynein recruitment to the nuclear surface, a critical step that is required for nucleus-centrosome coupling at M-phase entry and fidelity of meiotic divisions...
  10. Role of ORCA in DNA replication
    Supriya Gangadharan Prasanth; Fiscal Year: 2013
    ..Other than their bonafide roles in DNA replication, ORC proteins are required for heterochromatin organization, centrosome copy number maintenance, accurate cell cycle progression and cell division...
  11. The interaction of Chlamydia with the host cytoskeleton
    Scott S Grieshaber; Fiscal Year: 2012
    ..center (MTOC) of the cell, which ultimately leads to an intimate association between the inclusion and the host centrosome. The mature chlamydial inclusion remains associated with the centrosomes causing centrosome number defects, ..
  12. Modeling the genetic basis for human congenital heart disease in mice
    Cecilia W Lo; Fiscal Year: 2013
    ..Our screen recovered many genes encoding proteins in the cilia or centrosome, suggesting the cilium is a central disease pathway in CHD...
  13. ROCK II-mediated regulation of centrosome duplication / centrosome amplification
    Kenji Fukasawa; Fiscal Year: 2013
    ..of solid tumors and certain types of lymphoma and leukemia, and the strong association between occurrence of centrosome amplification and aneuploidy...
  14. Signaling by p21-activated protein kinases
    JONATHAN D CHERNOFF; Fiscal Year: 2010
    ..Paks in two specific processes that are germane to tumorigenesis: genomic stability (via regulation of centrosome function) and cell proliferation (via effects on elements in the ERK signal transduction cascade)...
  15. The role of DNA damage response signaling in chronic kidney disease
    Rannar Airik; Fiscal Year: 2013
    ..Recent work has identified NPHP as a "ciliopathy", caused by mutations in genes, whose proteins localize to the centrosome and/or primary cilium, and has generated a unifying pathogenic concept for NPHP-related ciliopathies (NPHP-RC)...
  16. The Control of Centriole Duplication and Degeneration
    Meng Fu Bryan Tsou; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The centrosome is essential for many cellular processes, including (i) formation of the mitotic spindle, (ii) cell polarity and asymmetric cell division, (iii) assembly of cilia and flagella, and (iv) ..
  17. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2013
    ..to growth and survival factors;Fbxl10 and Fbxl11 contribute to epigenetic regulation;Cyclin F/Fbxo1 prevents centrosome overduplication by targeting CP110 for degradation;and Fbxl3 is required to reset the circadian clock by ..
  18. Molecular mechanisms underlying chromosomal instability and aneuploidy
    Wei Dai; Fiscal Year: 2012
    ..it is enriched at the spindle poles and mitotic spindles during mitosis, suggesting a role for this protein in centrosome dynamics...
  19. DISSECTION OF THE DNA DAMAGE CHECKPOINT PATHWAYS
    Yolanda Sanchez; Fiscal Year: 2009
    ..advantage of the fact that cancer cells have defects in the response to DNA damage and/or in the coordination of centrosome duplication with DNA replication...
  20. Centrosomes and Hedgehog Signaling in Development and Polycystic Kidney Disease
    Hisham Bazzi; Fiscal Year: 2013
    ..Primary cilia use the centriole, the core of the centrosome, as a template...
  21. Mechanism controlling centrosome duplication
    Barbara E Tanos; Fiscal Year: 2013
    ..Deregulation of centrosome number contributes to genome instability, a hallmark of cancer...
  22. New Methods for the Synthesis of Neurological Agents and Other Heterocyclic Molec
    Larry E Overman; Fiscal Year: 2013
    ..contributions of Golgi organization and position to the regulation of protein trafficking, cell polarization, centrosome organization, and cell division...
  23. Regulation of Cytokinesis in Fission yeast.
    Dannel McCollum; Fiscal Year: 2013
    ..tumor suppression, and stem cell differentiation (Hippo/Lats), or growth promotion, chromosome congression and centrosome duplication (Ndr1/2)...
  24. The Nucleocytoskeleton in Progeria and Aging
    Howard J Worman; Fiscal Year: 2013
    ..resulting in defective nucleocytoskeletal connections and consequently alterations in nuclear movement and centrosome positioning...
  25. MICROTUBULE REGULATION
    Don W Cleveland; Fiscal Year: 2013
    ..The duplication of the centrosome is tightly controlled, and extra centrosomes can cause errors in spindle formation that lead to subsequent ..
  26. Regulation of Centrosome Assembly by Phosphorylation
    Mi Hye Song; Fiscal Year: 2012
    ..elegans embryo as an in vivo model to perform genetics-phosphoproteomic analyses of centrosome assembly. Among 5 essential centrosome factors in C...
  27. Centrosome and mitotic functions of ciliary proteins
    Stephen Doxsey; Fiscal Year: 2009
    ..RNAi-mediated depletion of the cilia protein IFT88 in zebrafish embryos and cultured cells disrupts centrosome/spindle pole integrity, astral microtubule organization and spindle organization;depletion of other IFT proteins ..
  28. Katanin p80: A Role for Regulation of Microtubule Severing in Cortical Developmen
    WEN FAN HU; Fiscal Year: 2013
    ..Mutations in genes causing microcephaly encode proteins that localize to the centrosome and pericentriolar matrix, suggesting that this is the seat of an important common pathway that regulates ..
  29. Aurora-A/BTAK/STK15 Oncoprotein in Mitotic Spindle Assembly and Checkpoint Respon
    Subrata Sen; Fiscal Year: 2012
    ..The results have revealed that Aurora-A is the key regulator of both kinetochore/chromatin and centrosome associated microtubule formation processes contributing to bipolar spindle assembly and that loss of Aurora-A ..
  30. A Role for PML in Genome Stability and DNA Damage Response
    Kun Sang Chang; Fiscal Year: 2012
    ..Our laboratory recently reported an important role for PML3 in centrosome duplication and genome stability...
  31. Role of Nucleo-cytoskeleton Interactions in Cell Migration
    Gregg G Gundersen; Fiscal Year: 2013
    ..tether the nucleus to moving actin filaments and treatments that disrupt TAN lines prevent nuclear movement, centrosome orientation and inhibit migration of cells into in vitro wounds...
  32. Function and Regulation of the Phosphorylation-Specific Prolyl lsomerase Pin 1
    Kun Ping Lu; Fiscal Year: 2010
    ..upstream oncogenic signal pathways, and for the coordination of some downstream cell cycle events such as centrosome duplication...
  33. OMX BLAZE High Speed Super Resolution Imaging System
    Aaron F Straight; Fiscal Year: 2012
    ..wide range of topics, including: meiotic chromosome segregation (Villeneuve);genetic recombination (Villeneuve);centrosome structure, function and duplication (Stearns);centromere and kinetochore assembly (Straight);biogenesis and ..
  34. FASEB SRC on Mitosis: Spindle Assembly and Function
    Claire E Walczak; Fiscal Year: 2012
    ..Mitotic spindle assembly;2. Quantitative approaches to mitosis;3. Centrosome structure and function;4. Kinetochore assembly and function;5. Chromosome structure and function;6...
  35. Centrosome Mis-Regulation and Blood Vessel Function
    Victoria L Bautch; Fiscal Year: 2013
    ..b>Centrosome duplication is normally tightly regulated to occur once and only once per cell cycle, and loss of this ..
  36. Polyploidy, aneuploidy and genome stability
    DAVID S PELLMAN; Fiscal Year: 2013
    ..grant that defined 'ploidy-specific lethality', where genes that are not essential in normal diploid cells become essential in polyploid cells or extra centrosome-containing cells that have a chromosomal instability phenotype.
  37. Cyclic AMP Mediation of Epithelial Cell Function
    JAMES RICHARD GOLDENRING; Fiscal Year: 2012
    ..Importantly, while previous investigations have focused attention on AKAP350 at the centrosome and the Golgi apparatus, our recent studies have led to the recognition that in most cells a large cytosolic ..
  38. The Mechanism of Pericentriolar Material Assembly During Centrosome Biogenesis
    Tomer Avidor-Reiss; Fiscal Year: 2013
    ..Defective centrosome biogenesis causes male infertility, numerous types of cancer, and various developmental disorders...
  39. Role of Polo-Like Kinase-1 in Melanocytic Transformation
    Nihal Ahmad; Fiscal Year: 2013
    ..family that contributes to multiple mitotic processes including the activation of the Cdk1/Cyclin B1 cascade, centrosome maturation, bipolar spindle formation and the regulation of Emi1 degradation at mitotic exit...
  40. Interaction Between SV40 Large T and p185 Cullin
    James A DeCaprio; Fiscal Year: 2011
    ..of Cul7 or Fbxw8 appears to promote genomic instability and increase the frequency of aneuploidy and aberrant centrosome number...
  41. HEF1 Coordination of Cell Cycle, Migration, and Invasion in Cancer
    Erica A Golemis; Fiscal Year: 2013
    ..HEF1 acts to assemble signaling complexes at focal adhesions in interphase cells, at the centrosome in pre-mitotic cells, and at the cilium in cells emerging from quiescence...
  42. Particulate Cr(VI) Toxicology in Human Lung Epithelial Cells and Fibroblasts
    John Pierce Wise; Fiscal Year: 2013
    ..Our preliminary data show that chronic exposure to particulate Cr(VI) induces centrosome amplification and spindle assembly checkpoint bypass, and thus, the goal of this research is to understand the ..
  43. Molecular and Cellular Mechanisms of Neocortical Neurogenesis
    Song Hai Shi; Fiscal Year: 2013
    ..dividing radial glial progenitor cells are differentially inherited b the two daughter cells dependent on the centrosome maturity and daughter cell fate specification...
  44. Non-random template DNA strand segregation in muscle progenitor cells
    GREGORY WILLIAM CHARVILLE; Fiscal Year: 2013
    ..Recent work has confirmed that asymmetric stem cell division involves non-random template DNA strand and centrosome segregation to one of two daughter cells...
  45. The Biology of Genetic Variants in Human Kidney Disease
    JOHN F O'TOOLE; Fiscal Year: 2013
    ..al. 2009). We have clearly shown that XPNPEP3 localizes to the mitochondria, rather than the primary cilia/centrosome/basal body complex (O'Toole, et al. 2010) as typical for other NPHP gene products...
  46. Mother Centriole Appendages Regulate the AMIS Compartment and Cilogenesis.
    Heidi Hehnly; Fiscal Year: 2013
    ..k.a. the centrosome) including the intraflagellar transport proteins (IFTs), the Bardet-Biedl syndrome complex that interacts with ..
  47. Regulation of cell polarity during neurulation
    RACHEL MELISSA BREWSTER; Fiscal Year: 2013
    ..In aim 2, we will investigate a novel role for Par3 in positioning the centrosome at the apical cortex during epithelialization...
  48. Mechanism of Chlamydia-induced centrosome amplification
    Ming Tan; Fiscal Year: 2010
    ..Recently, C. trachomatis has been shown to induce centrosome abnormalities in an infected cell, which is intriguing as centrosome abnormalities can lead to genomic ..
  49. Desmosomal Control of Cytoskeletal Organization
    Terry H Lechler; Fiscal Year: 2013
    ..intermediate filaments and microtubules through recruitment of a protein complex that is usually found at the centrosome. Some of the novel desmosomal proteins in this complex, including Lis1 and NDEL1, are known to control ..
  50. Zeiss Laser TIRF 3 microscope and live cell imaging system
    Joseph E Mazurkiewicz; Fiscal Year: 2010
    ..user group will apply this capability in several diverse areas of study: understanding how integrins regulate centrosome function and microtubule assembly during interphase and mitosis;the regulation of the assembly and disassembly ..
  51. Dissecting mechanism of centrosome attachment and segregation to spindle poles
    ELIF FIRAT; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The centrosome is a conserved organelle that organizes the microtubule network, and nucleates the primary cilium, a nexus for cell signaling pathways...
  52. Control of centrosome duplication and G1 arrest after prolonged prometaphase
    Greenfield Sluder; Fiscal Year: 2013
    ..Since mitotic fidelity depends upon the cell containing just two centrosomes, centrosome duplication must be under tight numerical and temporal control...
  53. Evaluation of HSET as a Novel Theranostic Target for Breast Cancer Therapy
    Ritu Aneja; Fiscal Year: 2013
    ..We rationalize that depleting breast cancer cells of their centrosome-clustering arsenal will result in cells with highly aberrant multipolar spindle, which will serve as a "point of ..
  54. Using p53 Knock-In Mice to Understand p53's Role in Pancreatic Cancer
    Laura D Attardi; Fiscal Year: 2010
    ..regulating transcriptional repression, DNA replication and recombination, mitochondrial membrane integrity, and centrosome duplication...
  55. Asymmetric chromosome strand inheritance during stem cell division in Drosophila
    Swathi Yadlapalli; Fiscal Year: 2013
    ..Recently, it was hypothesized by many researchers that the mother centrosome, which is stereotypically retained within some stem cells, might be used as a means to anchor the immortal DNA ..
  56. Informatics methods for identifying breast cancer control genes and proteins
    Jeffrey D Parvin; Fiscal Year: 2013
    ..BRCA1 and BRCA2 gene products both regulate cell division pathways that involve DNA repair and centrosome duplication, and their expression is correlated in microarray analyses in many cell types...
  57. Analysis of intracellular signaling in angiogenesis
    Jun Lin Guan; Fiscal Year: 2013
    ..a novel role for S732 phosphorylation of FAK in promoting EC proliferation and angiogenesis by the regulation of centrosome functions during mitosis. We have also created two different FAK mutant knockin mouse models...
  58. MPS1 kinase in the Spindle Pole Cycle
    Mark Winey; Fiscal Year: 2013
    ..Failure in centrosome duplication or function leads to genomic instability and contributes to cellular transformation...
  59. Mitotic Response to DNA damage
    WILLIAM EDWARD THEURKAUF; Fiscal Year: 2010
    ..We have found that mitotic catastrophe in early Drosophila embryos is linked to centrosome inactivation, chromosome condensation defects, and midbody assembly failures...
  60. Regulation of the Mps1 Protein Kinase and Centrosome Duplication
    Harold A Fisk; Fiscal Year: 2012
    The mammalian Mps1 protein kinase is a key regulator of centrosome duplication and is the focus of our proposed project...
  61. A model system to study the tumor suppressor APC
    Mark Peifer; Fiscal Year: 2013
    ..In this Aim we will determine how APC and its partners act to regulate centrosome migration and thus ensure high fidelity chromosome segregation, and explore how Chk2 and other checkpoint ..
  62. Regulation of Microtubules by Rho GTPases
    Gregg G Gundersen; Fiscal Year: 2013
    ..MTs in wound edge migrating fibroblasts: formation of a subset of unusually stable MTs and reorientation of the centrosome. In previous grant periods, we identified many of the factors in the pathways that are activated by these ..
  63. CENTROSOME DEFECTS AS CAUSES OF MALE INFERTILITY
    Gerald Schatten; Fiscal Year: 1999
    ..the oocyte, sperm-oocyte plasma membrane fusion, and the cytoplasmic events mediated by the sperm nucleus and centrosome, which lead to the culmination of the fertilization process -- the merging of the parental genomes...
  64. Mechanisms of Centrosome Reproduction in Animal Cells
    EDWARD HINCHCLIFFE; Fiscal Year: 2009
    ..Bipolar spindle assembly is directed by the duplication of the centrosome, which serves as the major microtubule-organizing center in mammalian cells...
  65. FUNCTION OF THE C ELEGANS GENE LIN5 IN MITOSIS
    Sander van den Heuvel; Fiscal Year: 2003
    ..the molecular basis of the mitotic machinery: what are the components used and how do they act to accomplish centrosome duplication, spindle assembly, chromosome movement, sister chromatid separation and a correct timing of all the ..
  66. X-LINKED RETINITIS PIGMENTOSA
    Hemant Khanna; Fiscal Year: 2009
    ..mutations are detected in the RPGRORF15 isoforms that primarily localize to ciliary axoneme, basal body and centrosome. RPGR interacts with several ciliary and microtubule transport proteins...