2016
DOI: 10.1073/pnas.1607421113
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Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore

Abstract: Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping h… Show more

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Cited by 10 publications
(12 citation statements)
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“…In our assays, TPR could easily be pulled down by Ndc80C Bonsai . Consistent with the strong Ndc80C and TPR interaction, previous studies demonstrated the importance of TPR in mediating Mps1 kinetochore localization ( Thebault et al, 2012 ; Nijenhuis et al, 2013 ; Marquardt et al, 2016 ). Thus, we conclude that the TPR domain is involved in mediating Mps1–Ndc80C interaction directly.…”
Section: Discussionsupporting
confidence: 75%
“…In our assays, TPR could easily be pulled down by Ndc80C Bonsai . Consistent with the strong Ndc80C and TPR interaction, previous studies demonstrated the importance of TPR in mediating Mps1 kinetochore localization ( Thebault et al, 2012 ; Nijenhuis et al, 2013 ; Marquardt et al, 2016 ). Thus, we conclude that the TPR domain is involved in mediating Mps1–Ndc80C interaction directly.…”
Section: Discussionsupporting
confidence: 75%
“…BUB1 and BUBR1 share a common architecture: a conserved N-terminal domain, a middle nonconserved domain that contains the binding region for the mitotic checkpoint protein BUB3, and a C-terminal serine/threonine kinase domain. The N-terminal regions of BUB1 and BUBR1 (and also MPS1) contain a divergent arrangement of the TPR (tetratricopeptide repeat) motif (Bolanos-Garcia et al 2009, D'Arcy et al 2010, Lee et al 2012) that mediates recruitment of the proteins to the kinetochore Krenn et al 2012Krenn et al , 2014Marquardt et al 2016;Nijenhuis et al 2013;Thebault et al 2012). The middle domain of BUB1 and BUBR1 contains the GLE2p-binding sequence (GLEBS)-like motif, which is located within the region E3 ubiquitin ligase: a class of enzymes that catalyze the final step of ubiquitination, namely, the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a protein substrate implicated in BUB3 binding.…”
Section: Figurementioning
confidence: 99%
“…Critical to human Mps1 activity is its localization to the kinetochore, which in human cells is primarily mediated by the non-catalytic NTE (N-terminal extension), with a minor contribution from the MR (middle region). Together, these regions sandwich a TPR (tetratricopeptide repeat) motif, which also plays a role in Mps1 localization [ 29 , 30 , 31 , 32 , 33 , 34 ]. The NTE is a region of about fifty amino acids at the extreme N terminus; it is rather poorly conserved and lacks clear structural and functional domains.…”
Section: Introductionmentioning
confidence: 99%