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  • Suijkerbuijk, Saskia J EMolecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands (author)

The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • Cambridge, United States :Cell Press,2012
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:liu-143665
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143665URI
  • https://doi.org/10.1016/j.devcel.2012.03.009DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution, followed by parallel subfunctionalization in which preservation of the ancestral, amino-terminal KEN box or kinase domain was mutually exclusive. In one exception, vertebrate BUBR1-defined by the KEN box-preserved the kinase domain but allowed nonconserved degeneration of catalytic motifs. Although BUBR1 evolved to a typical pseudokinase in some vertebrates, it retained the catalytic triad in humans. However, we show that putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation. Instead, residues that interact with ATP in conventional kinases are essential for conformational stability in BUBR1. We propose that parallel evolution of BUBR1 orthologs rendered its kinase function dispensable in vertebrates, producing an unusual, triad-containing pseudokinase.

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  • van Dam, Teunis J PTheoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands; Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (author)
  • Karagöz, G ElifCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands (author)
  • von Castelmur, EleonoreDepartment of Biochemistry, NKI, Amsterdam, The Netherlands(Swepub:liu)elevo74 (author)
  • Hubner, Nina CMolecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands (author)
  • Duarte, Afonso M SCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands (author)
  • Vleugel, MathijsMolecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands (author)
  • Perrakis, AnastassisDepartment of Biochemistry, NKI, Amsterdam, The Netherlands (author)
  • Rüdiger, Stefan G DCellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands (author)
  • Snel, BerendTheoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands (author)
  • Kops, Geert J P LMolecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands; Department of Medical Oncology, UMC Utrecht, Utrecht, The Netherlands (author)
  • Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The NetherlandsTheoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands; Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (creator_code:org_t)

Related titles

  • In:Developmental CellCambridge, United States : Cell Press22:6, s. 1321-13291534-58071878-1551

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