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The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase

Suijkerbuijk, Saskia J E (författare)
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
van Dam, Teunis J P (författare)
Theoretical 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
Karagöz, G Elif (författare)
Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
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von Castelmur, Eleonore (författare)
Department of Biochemistry, NKI, Amsterdam, The Netherlands
Hubner, Nina C (författare)
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
Duarte, Afonso M S (författare)
Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
Vleugel, Mathijs (författare)
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
Perrakis, Anastassis (författare)
Department of Biochemistry, NKI, Amsterdam, The Netherlands
Rüdiger, Stefan G D (författare)
Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands
Snel, Berend (författare)
Theoretical Biology and Bioinformatics, Department of Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands
Kops, Geert J P L (författare)
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands; Department of Medical Oncology, UMC Utrecht, Utrecht, The Netherlands
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 (creator_code:org_t)
Cambridge, United States : Cell Press, 2012
2012
Engelska.
Ingår i: Developmental Cell. - Cambridge, United States : Cell Press. - 1534-5807 .- 1878-1551. ; 22:6, s. 1321-1329
Relaterad länk:
http://www.cell.com/...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

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