ArticleProceedings of the National Academy of Sciences of the United States of America2015
Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Proximity-based activation of AURORA A by MPS1 potentiates error correction.Current biology : CB · 2025Article
- Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.Journal of molecular cell biology · 2024Review
- Organization of microtubule plus-end dynamics by phase separation in mitosis.Journal of molecular cell biology · 2024Article
- Measuring and modeling the dynamics of mitotic error correction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fluorescence complementation-based FRET imaging reveals centromere assembly dynamics.Molecular biology of the cell · 2024Article
- Phosphorylation of Bub1 by Mph1 promotes Bub1 signaling at the kinetochore to ensure accurate chromosome segregation.The Journal of biological chemistry · 2024Article
- Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.Journal of molecular cell biology · 2023Article
- Phosphorylation of CENP-R by Aurora B regulates kinetochore-microtubule attachment for accurate chromosome segregation.Journal of molecular cell biology · 2022Article
- Structural insights into human CCAN complex assembled onto DNA.Cell discovery · 2022Article
- CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- TTK inhibition increases cisplatin sensitivity in high-grade serous ovarian carcinoma through the mTOR/autophagy pathway.Cell death & disease · 2021Article
- Multiple functions of reversine on the biological characteristics of sheep fibroblasts.Scientific reports · 2021Article
- Chemical tools for dissecting cell division.Nature chemical biology · 2021Review
- Phase separation drives decision making in cell division.The Journal of biological chemistry · 2020Review
- The whole is greater than the sum of its parts: at the intersection of order, disorder, and kinetochore function.Essays in biochemistry · 2020Review
- Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly.Journal of molecular cell biology · 2020Article
- Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling.Journal of molecular cell biology · 2020Article
- TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination.The Journal of clinical investigation · 2020Article
- Autophosphorylation is sufficient to release Mps1 kinase from native kinetochores.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment.Molecular biology of the cell · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.