ArticleThe Journal of biological chemistry2010
MST1 promotes apoptosis through phosphorylation of histone H2AX.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
- The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.Cell · 2021Trial
- Histone modification-mediated epigenetic regulation in AKI-to-CKD transition: a cell-type-specific perspective.Journal of translational medicine · 2025Review
- Crosstalk between MST1-Hippo and Wnt/β-Catenin, Notch, and PI3K/Akt pathways in cardiac physiology and pathology.Journal of physiology and biochemistry · 2025Review
- Harnessing the FGFR2/NF2/YAP signaling-dependent necroptosis to develop an FGFR2/IL-8 dual blockade therapeutic strategy.Nature communications · 2025Article
- Histone Phosphorylation in DNA Damage Response.International journal of molecular sciences · 2025Review
- Activation of the conserved Hippo kinases by inflammasome-triggered proteolytic cleavage controls programmed cell death in macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mammalian STE20-like kinase 1 inhibits synoviocytes activation in rheumatoid arthritis through mitochondrial dysfunction mediated by SIRT3/mTOR axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Picrasidine I Triggers Heme Oxygenase-1-Induced Apoptosis in Nasopharyngeal Carcinoma Cells via ERK and Akt Signaling Pathways.International journal of molecular sciences · 2022Article
- Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers.The Journal of clinical investigation · 2022Article
- MST1 controls murine neutrophil homeostasisFrontiers in immunology · 2022Article
- Function and mechanism of histone β-hydroxybutyrylation in health and disease.Frontiers in immunology · 2022Review
- Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice.Molecules (Basel, Switzerland) · 2020Article
- MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer.PLoS pathogens · 2020Article
- Article
- MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells.International journal of molecular sciences · 2019Article
- The Roles of P53 and Its Family Proteins, P63 and P73, in the DNA Damage Stress Response in Organogenesis-Stage Mouse Embryos.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Role of novel histone modifications in cancer.Oncotarget · 2018Review
- Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate.Journal of molecular biology · 2017Review
- MST1/MST2 Protein Kinases: Regulation and Physiologic Roles.Biochemistry · 2016Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
MST1 (mammalian STE20-like kinase 1) is a serine/threonine kinase that is cleaved and activated by caspases during apoptosis. Overexpression of MST1 induces apoptotic morphological changes such as chromatin condensation, but the mechanism is not clear. Here we show that MST1 induces apoptotic chromatin condensation through its phosphorylation of histone H2AX at Ser-139. During etoposide-induced apoptosis in Jurkat cells, the cleavage of MST1 directly corresponded with strong H2AX phosphorylation. In vitro kinase assay results showed that MST1 strongly phosphorylates histone H2AX. Western blot and kinase assay results with a mutant S139A H2AX confirmed that MST1 phosphorylates H2AX at Ser-139. Direct binding of MST1 and H2AX can be detected when co-expressed in HEK293 cells and was also confirmed by an endogenous immunoprecipitation study. When overexpressed in HeLa cells, both the MST1 full-length protein and the MST1 kinase domain (MST1-NT), but not the kinase-negative mutant (MST1-NT-KN), could induce obvious endogenous histone H2AX phosphorylation. The caspase-3 inhibitor benzyloxycarbonyl-DEVD-fluoromethyl ketone (Z-DEVD-fmk) attenuates phosphorylation of H2AX by MST1 but cannot inhibit MST1-NT-induced histone H2AX phosphorylation, indicating that cleaved MST1 is responsible for H2AX phosphorylation during apoptosis. Histone H2AX phosphorylation and DNA fragmentation were suppressed in MST1 knockdown Jurkat cells after etoposide treatment. Taken together, our data indicated that H2AX is a substrate of MST1, which functions to induce apoptotic chromatin condensation and DNA fragmentation.
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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.