Uncovering the Molecular Machinery of the Human Spindle-An Integration of Wet and Dry Systems Biology

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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  • Author: Rojas, Ana M.

    Centro Nacional de Investigaciones Oncológicas, Structural Biology and Biocomputing Programme, Spain

  • Author: Santamaria, Anna

    Max Planck Institute for Biochemistry, Department of Cell Biology, Germany

  • Author: Malik, Rainer

    Max Planck Institute for Biochemistry, Department of Cell Biology, Germany

  • Author: Jensen, Thomas Skot

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark

  • Author: Korner, Roman

    Department of Cellular Biochemistry, Max-Planck Institute of Biochemistry, Germany

  • Author: Morilla, Ian

    Department of Biochemistry and Molecular Biology, University of Malaga, Spain

  • Author: de Juan, David

    Centro Nacional de Investigaciones Oncológicas, Structural Biology and Biocomputing Programme, Spain

  • Author: Krallinger, Martin

    Centro Nacional de Investigaciones Oncológicas, Structural Biology and Biocomputing Programme, Spain

  • Author: Hansen, Daniel Aaen

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark

  • Author: Hoffmann, Robert Daniel

    Memorial Sloan-Kettering Cancer Center, Computational Biology Center, United States

  • Author: Lees, Jonathan

    University College London, United Kingdom

  • Author: Reid, Adam

    University College London, United Kingdom

  • Author: Yeats, Corin

    University College London, United Kingdom

  • Author: Wehner, Anja

    Max Planck Institute for Biochemistry, Department of Cell Biology, Germany

  • Author: Elowe, Sabine

    Max Planck Institute for Biochemistry, Department of Cell Biology, Germany

  • Author: Clegg, Andrew B.

    University College London, United Kingdom

  • Author: Brunak, Soren

    CFB - Metagenomic Systems Biology, Novo Nordisk Foundation Center for Biosustainability, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark

  • Author: Nigg, Erich A.

    Max Planck Institute for Biochemistry, Department of Cell Biology, Germany

  • Author: Orengo, Christine

    University College London, United Kingdom

  • Author: Valencia, Alfonso

    Centro Nacional de Investigaciones Oncológicas, Structural Biology and Biocomputing Programme, Spain

  • Author: Ranea, Juan A. G.

    Department of Biochemistry and Molecular Biology, University of Malaga, Spain

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The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub'', proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system.
Original languageEnglish
JournalP L o S One
Publication date2012
Volume7
Issue3
Pagese31813
ISSN1932-6203
DOIs
StatePublished

Bibliographical note

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 2.5, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly cited.

CitationsWeb of Science® Times Cited: 4

Keywords

  • BIOLOGY, MITOTIC PROGRESSION, GENE-FUNCTION, CELL-CYCLE, PLK1-DEPENDENT PHOSPHORYLATION, ASSEMBLY CHECKPOINT, MAMMALIAN-CELLS, PROTEIN, COMPLEX, KINETOCHORE, MITOSIS
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