ArticleMolecular biology of the cell2007
Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 89 citations in OpenAlex.
- Integrated analysis of hub genes and intrinsically disordered regions in triple-negative breast cancer.Journal, genetic engineering & biotechnology · 2024Article
- Steroidogenic Factor-1 form and function: From phospholipids to physiology.Advances in biological regulation · 2024Review
- CDK2 inhibition disorders centrosome stoichiometry and alters cellular outcomes in aneuploid cancer cells.Cancer biology & therapy · 2023Article
- Phosphotyrosine picked threonine kinase stimulates proliferation of human osteosarcoma cellsArchives of medical science : AMS · 2022Article
- MPS1 is involved in the HPV16-E7-mediated centrosomes amplification.Cell division · 2021Article
- Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment.Molecular biology of the cell · 2019Article
- TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer.Oncogenesis · 2018Article
- Centrosome aberrations and chromosome instability contribute to tumorigenesis and intra-tumor heterogeneity.Journal of cancer metastasis and treatment · 2018Article
- Antizyme inhibitor 1: a potential carcinogenic molecule.Cancer science · 2017Review
- The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation.Cell cycle (Georgetown, Tex.) · 2016Review
- Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Centrosome - a promising anti-cancer target.Biologics : targets & therapy · 2016Review
- Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function.Molecular biology of the cell · 2015Article
- Spatial regulation of the spindle assembly checkpoint and anaphase-promoting complex in Aspergillus nidulans.Molecular microbiology · 2015Article
- Involvement of Antizyme Characterized from the Small Abalone Haliotis diversicolor in Gonadal Development.PloS one · 2015Article
- Quantitative immunofluorescence assay to measure the variation in protein levels at centrosomes.Journal of visualized experiments : JoVE · 2014Article
- Show me your license, please: deregulation of centriole duplication mechanisms that promote amplification.Cellular and molecular life sciences : CMLS · 2013Review
- VDAC3 and Mps1 negatively regulate ciliogenesis.Cell cycle (Georgetown, Tex.) · 2013Article
- Phosphorylation of Mps1 by BRAFV600E prevents Mps1 degradation and contributes to chromosome instability in melanoma.Oncogene · 2013Article
- Steroidogenic factor 1 (NR5A1) maintains centrosome homeostasis in steroidogenic cells by restricting centrosomal DNA-dependent protein kinase activation.Molecular and cellular biology · 2013Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Supernumerary centrosomes promote the assembly of abnormal mitotic spindles in many human tumors. In human cells, overexpression of the cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication. Cdk2 activity protects the Mps1 protein kinase from proteasome-mediated degradation, and we demonstrate here that Mps1 mediates cyclin A-dependent centrosome reduplication. Overexpression of cyclin A or a brief proteasome inhibition increases the centrosomal levels of Mps1, whereas depletion of Cdk2 leads to the proteasome-dependent loss of Mps1 from centrosomes only. When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. In contrast, phosphomimetic mutations at T468 or deletion of the region surrounding T468 prevent the proteasome-dependent removal of Mps1 from centrosomes in the absence of Cdk2 activity. Moreover, cyclin A-dependent centrosome reduplication requires Mps1, and these stabilizing Mps1 mutations cause centrosome reduplication, bypassing cyclin A. Together, our data demonstrate that the region surrounding T468 contains a motif that regulates the accumulation of Mps1 at centrosomes. We suggest that phosphorylation of T468 attenuates the degradation of Mps1 at centrosomes and that preventing this degradation is necessary and sufficient to cause centrosome reduplication in human cells.
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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.