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

Ana M. Rojas, Anna Santamaria, Rainer Malik, Thomas Skot Jensen, Roman Korner, Ian Morilla, David de Juan, Martin Krallinger, Daniel Aaen Hansen, Robert Daniel Hoffmann, Jonathan Lees, Adam Reid, Corin Yeats, Anja Wehner, Sabine Elowe, Andrew B. Clegg, Soren Brunak, Erich A. Nigg, Christine Orengo, Alfonso ValenciaJuan A. G. Ranea

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Abstract

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
Volume7
Issue number3
Pages (from-to)e31813
ISSN1932-6203
DOIs
Publication statusPublished - 2012

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.

Keywords

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

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