ArticleOncogene2013
Phosphorylation of Mps1 by BRAFV600E prevents Mps1 degradation and contributes to chromosome instability in melanoma.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Community detection in empirical kinase networks identifies new potential members of signalling pathways.PLoS computational biology · 2023Article
- Chromosome instability-associated prognostic signature and cluster investigation for cutaneous melanoma cases.IET systems biology · 2023Article
- Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis.Nature communications · 2022Article
- Inactivation of the Hippo tumor suppressor pathway promotes melanoma.Nature communications · 2022Article
- The Spindle Assembly Checkpoint Functions during Early Development in Non-Chordate Embryos.Cells · 2020Article
- Mps1 is associated with the BRAFOncology letters · 2019Article
- New insights into intranuclear inclusions in thyroid carcinoma: Association with autophagy and with BRAFV600E mutation.PloS one · 2019Article
- Mps1 is associated with the BRAFOncology letters · 2018Article
- A look into centrosome abnormalities in colon cancer cells, how they arise and how they might be targeted therapeutically.Biochemical pharmacology · 2018Review
- Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer.World journal of gastroenterology · 2017Article
- Gene expression profiling of anti-CTLA4-treated metastatic melanoma in patients with treatment-induced autoimmunity.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- 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
- Studying mechanisms of cAMP and cyclic nucleotide phosphodiesterase signaling in Leydig cell function with phosphoproteomics.Cellular signalling · 2016Article
- Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.GigaScience · 2016Article
- Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.PLoS pathogens · 2015Article
- Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age.Oncotarget · 2015Article
- Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma.American journal of human genetics · 2015Article
- TSH signaling overcomes B-RafV600E-induced senescence in papillary thyroid carcinogenesis through regulation of DUSP6.Neoplasia (New York, N.Y.) · 2014Article
- TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.Molecular oncology · 2014Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating BRAF mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. BRAF(V600E) induces centrosome amplification and spindle abnormalities that result in aneuploidy. We find modification of Mps1 is critical for contributing to centrosome amplification and chromosome instability induced by BRAF(V600E). Phosphorylation of Mps1 at residue S281 induced by BRAF(V600E) stabilizes Mps1 protein by preventing its ubiquitination by APC/C and subsequent degradation, allowing the non-degraded protein to accumulate at centrosomes. Cells in which endogenous Mps1 was replaced with a phospho-mimetic Mps1 mutant are viable but amplify centrosomes and missegregate chromosomes frequently. Importantly, analysis of tumor micro arrays revealed that phospho-MAPK and S281-phosphorylated Mps1 were highly correlated in human melanoma tissues, implying that MAPK contributes to defects in the degradation of Mps1 in situ. We propose that continuously activated BRAF(V600E) signaling may be a possible mechanism for the deregulation of Mps1 stability and kinase activity in human tumors, and that persistent phosphorylation of Mps1 through BRAF(V600E) signaling is a key event in disrupting the control of centrosome duplication and chromosome stability that may contribute to tumorigenesis. Our findings raise the possibility that targeting the oncogenic BRAF and S281-phosphorylated Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment.
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