ArticleNucleic acids research2016
Requirement for human Mps1/TTK in oxidative DNA damage repair and cell survival through MDM2 phosphorylation.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 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
- Rewiring mitotic checkpoint control via Mps1 inhibition overcomes DNA repair-mediated resistance in glioblastoma.The Journal of biological chemistry · 2026Article
- XYL-1 and Olaparib Synergistically Inhibit the Growth of Pancreatic Cancer by Suppressing the SCD1/BRCA1 Signaling Pathway.Molecules (Basel, Switzerland) · 2026Article
- TTK activates ATR through RPA2 phosphorylation to promote olaparib resistance in ovarian cancer.Communications biology · 2025Article
- Targeting TTK Inhibits Tumorigenesis of T-Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the Therapeutic Implications of Co-Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer.Pharmaceutics · 2024Review
- Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer.Molecular therapy. Oncology · 2024Review
- Monopolar spindle 1 contributes to tamoxifen resistance in breast cancer through phosphorylation of estrogen receptor α.Breast cancer research and treatment · 2023Article
- BMAL1-TTK-H2Bub1 loop deficiency contributes to impaired BM-MSC-mediated bone formation in senile osteoporosis.Molecular therapy. Nucleic acids · 2023Article
- Comprehensive analysis of the expression and prognosis for RAI2: A promising biomarker in breast cancer.Frontiers in oncology · 2023Article
- Phosphotyrosine picked threonine kinase stimulates proliferation of human osteosarcoma cellsArchives of medical science : AMS · 2022Article
- Genotoxicity-Stimulated and CYLD-Driven Malignant Transformation.Cancer management and research · 2022Article
- Identification of an integrated kinase-related prognostic gene signature associated with tumor immune microenvironment in human uterine corpus endometrial carcinoma.Frontiers in oncology · 2022Article
- The essential roles of Mps1 in spermatogenesis and fertility in mice.Cell death & disease · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Review
- Mitotic and DNA Damage Response Proteins: Maintaining the Genome Stability and Working for the Common Good.Frontiers in cell and developmental biology · 2021Review
- Chromosomal instability upregulates interferon in acute myeloid leukemia.Genes, chromosomes & cancer · 2020Article
- TTK regulates proliferation and apoptosis of gastric cancer cells through the Akt-mTOR pathway.FEBS open bio · 2020Article
- TTK, CDC25A, and ESPL1 as Prognostic Biomarkers for Endometrial Cancer.BioMed research international · 2020Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human Mps1 (hMps1) is a protein kinase essential for mitotic checkpoints and the DNA damage response. Here, we present new evidence that hMps1 also participates in the repair of oxidative DNA lesions and cell survival through the MDM2-H2B axis. In response to oxidative stress, hMps1 phosphorylates MDM2, which in turn promotes histone H2B ubiquitination and chromatin decompaction. These events facilitate oxidative DNA damage repair and ATR-CHK1, but not ATM-CHK2 signaling. Depletion of hMps1 or MDM2 compromised H2B ubiquitination, DNA repair and cell survival. The impairment could be rescued by re-expression of WT but not the phospho-deficient MDM2 mutant, supporting the involvement of hMps1-dependent MDM2 phosphorylation in the oxidative stress response. In line with these findings, localization of RPA and base excision repair proteins to damage foci also requires MDM2 and hMps1. Significantly, like MDM2, hMps1 is upregulated in human sarcoma, suggesting high hMps1 and MDM2 expression may be beneficial for tumors constantly challenged by an oxidative micro-environment. Our study therefore identified an hMps1-MDM2-H2B signaling axis that likely plays a relevant role in tumor 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.