ArticleCurrent biology : CB2018
Mps1 Phosphorylates Its N-Terminal Extension to Relieve Autoinhibition and Activate the Spindle Assembly Checkpoint.
Article in Current biology : CB, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Targeting TTK Inhibits Tumorigenesis of T-Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Kinetochore-catalyzed MCC formation: A structural perspective.IUBMB life · 2023Article
- Article
- Computational Biology Dynamics of Mps1 Kinase Molecular Interactions with Isoflavones Reveals a Chemical Scaffold with Potential to Develop New Therapeutics for the Treatment of Cancer.International journal of molecular sciences · 2022Article
- TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma.BMC cancer · 2022Article
- Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021Review
- Kinetochore phosphatases suppress autonomous Polo-like kinase 1 activity to control the mitotic checkpoint.The Journal of cell biology · 2020Article
- Phosphoproteomics Meets Chemical Genetics: Approaches for Global Mapping and Deciphering the Phosphoproteome.International journal of molecular sciences · 2020Review
- Mps1 dimerization and multisite interactions with Ndc80 complex enable responsive spindle assembly checkpoint signaling.Journal of molecular cell biology · 2020Article
- Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56.The Journal of cell biology · 2019Article
- A crystal structure of the human protein kinase Mps1 reveals an ordered conformation of the activation loop.Proteins · 2019Article
- Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores.Cells · 2019Review
- Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis.Open biology · 2018Review
- Kinase and Phosphatase Cross-Talk at the Kinetochore.Frontiers in cell and developmental biology · 2018Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a "prone-to-autophosphorylate" Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells.
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