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A TPR domain-containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B

Nijenhuis, Wilco (författare)
Department of Molecular Cancer Research, Department of Medical Oncology, and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, Netherlands
von Castelmur, Eleonore (författare)
Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, Netherlands
Littler, Dene (författare)
Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, Netherlands
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De Marco, Valeria (författare)
Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, Netherlands
Tromer, Eelco (författare)
Department of Molecular Cancer Research, Department of Medical Oncology, and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, Netherlands
Vleugel, Mathijs (författare)
Department of Molecular Cancer Research, Department of Medical Oncology, and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, Netherlands
van Osch, Maria H J (författare)
Department of Molecular Cancer Research, Department of Medical Oncology, and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, Netherlands
Snel, Berend (författare)
Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands
Perrakis, Anastassis (författare)
Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, Netherlands
Kops, Geert J P L (författare)
Department of Molecular Cancer Research, Department of Medical Oncology, and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, Netherlands
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 (creator_code:org_t)
2013-04-08
2013
Engelska.
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 201:2, s. 217-231
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B-dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.

Ämnesord

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

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