ArticleThe Journal of biological chemistry2010
Degradation of the human mitotic checkpoint kinase Mps1 is cell cycle-regulated by APC-cCdc20 and APC-cCdh1 ubiquitin ligases.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- MPS1 inhibition as an anticancer strategy: where do we stand?Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026Review
- Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic Development of theACS omega · 2025Article
- Targeting APC/C Ubiquitin E3-Ligase Activation with Pyrimidinethylcarbamate Apcin Analogues for the Treatment of Breast Cancer.Biomolecules · 2024Article
- Cand2 inhibits CRL-mediated ubiquitination and suppresses autophagy to facilitate pathogenicity of phytopathogenic fungi.Plant communications · 2024Article
- MPS1 is involved in the HPV16-E7-mediated centrosomes amplification.Cell division · 2021Article
- Hsp90 chaperone code and the tumor suppressor VHL cooperatively regulate the mitotic checkpoint.Cell stress & chaperones · 2021Article
- Mitotic and DNA Damage Response Proteins: Maintaining the Genome Stability and Working for the Common Good.Frontiers in cell and developmental biology · 2021Review
- Review
- Mitotic slippage is determined by p31Oncogene · 2020Article
- Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma.Nature communications · 2019Article
- Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis.Open biology · 2018Review
- A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer.Theranostics · 2018Article
- APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.Cell cycle (Georgetown, Tex.) · 2017Article
- Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.British journal of cancer · 2017Article
- Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk.Radiology and oncology · 2016Article
- Phosphatidylinositol-4-phosphate 5-Kinase 1α Modulates Ribosomal RNA Gene Silencing through Its Interaction with Histone H3 Lysine 9 Trimethylation and Heterochromatin Protein HP1-α.The Journal of biological chemistry · 2015Article
- Global Phosphoproteomic Mapping of Early Mitotic Exit in Human Cells Identifies Novel Substrate Dephosphorylation Motifs.Molecular & cellular proteomics : MCP · 2015Article
- Targeting Cdc20 as a novel cancer therapeutic strategy.Pharmacology & therapeutics · 2015Review
- A putative N-terminal nuclear export sequence is sufficient for Mps1 nuclear exclusion during interphase.BMC cell biology · 2015Article
- Spatial regulation of the spindle assembly checkpoint and anaphase-promoting complex in Aspergillus nidulans.Molecular microbiology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mps1 is a dual specificity protein kinase with key roles in regulating the spindle assembly checkpoint and chromosome-microtubule attachments. Consistent with these mitotic functions, Mps1 protein levels fluctuate during the cell cycle, peaking at early mitosis and abruptly declining during mitotic exit and progression into the G(1) phase. Although evidence in budding yeast indicates that Mps1 is targeted for degradation at anaphase by the anaphase-promoting complex (APC)-c(Cdc20) complex, little is known about the regulatory mechanisms that govern Mps1 protein levels in human cells. Here, we provide evidence for the ubiquitin ligase/proteosome pathway in regulating human Mps1 levels during late mitosis through G(1) phase. First, we showed that treatment of HEK 293T cells with the proteosome inhibitor MG132 resulted in an increase in both the polyubiquitination and the accumulation of Mps1 protein levels. Next, Mps1 was shown to co-precipitate with APC and its activators Cdc20 and Cdh1 in a cell cycle-dependent manner. Consistent with this, overexpression of Cdc20 or Cdh1 led to a marked reduction of endogenous Mps1 levels during anaphase or G(1) phase, respectively. In contrast, depletion of Cdc20 or Cdh1 by RNAi treatment both led to the stabilization of Mps1 protein during mitosis or G(1) phase, respectively. Finally, we identified a single D-box motif in human Mps1 that is required for its ubiquitination and degradation. Failure to appropriately degrade Mps1 is sufficient to trigger centrosome amplification and mitotic abnormalities in human cells. Thus, our results suggest that the sequential actions of the APC-c(Cdc20) and APC-c(Cdh1) ubiquitin ligases regulate the clearance of Mps1 levels and are critical for Mps1 functions during the cell cycle in human cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.