ArticleNature communications2018
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- The Host Cell Factor Phosphatase-2A Subunit PR130 Restricts Replication of Herpes Simplex Virus Type-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Current Research in Polypharmacology for Cancer Treatment Using Dual-Target Histone Deacetylase Inhibitors.International journal of molecular sciences · 2026Review
- Endothelial progenitor cell susceptibility to DNA damaging and DDR-modulating compounds determines endothelial differentiation accuracy.Stem cell research & therapy · 2026Article
- Amelioration of acute liver failure by a cinnamic acid derivative through inhibition of the ROS-NETosis axis.Molecular biomedicine · 2026Article
- Multiple Regulatory Mechanisms of Post-Translational Modifications and Therapeutic Potential of Mitotic Catastrophe.International journal of molecular sciences · 2026Review
- MiR-31 suppresses lung adenocarcinoma cell proliferation through CDK1 and E2F2-mediated cell cycle arrest.Discover oncology · 2026Article
- Identification of a Proteolysis-Targeting-Chimera that Addresses Activated Checkpoint Kinase-1 Reveals its Non-Catalytic Functions in Tumor Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- The deacetylases HDAC1/HDAC2 control JAK2Signal transduction and targeted therapy · 2025Article
- Article
- Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.Molecular neurobiology · 2025Article
- BML-281 promotes neuronal differentiation by modulating Wnt/CaMolecular and cellular biochemistry · 2024Article
- Pharmacological degradation of ATR induces antiproliferative DNA replication stress in leukemic cells.Molecular oncology · 2024Article
- Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Discovery of novel and highly potent dual-targeting PKMYT1/HDAC2 inhibitors for hepatocellular carcinoma through structure-based virtual screening and biological evaluation.Frontiers in pharmacology · 2024Article
- GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage.Nucleic acids research · 2023Article
- The epigenetic modifier HDAC2 and the checkpoint kinase ATM determine the responses of microsatellite instable colorectal cancer cells to 5-fluorouracil.Cell biology and toxicology · 2023Article
- Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor.Oncogene · 2023Article
- Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway.BMC neuroscience · 2023Article
- VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show that the histone deacetylases HDAC1/HDAC2 sustain the phosphorylation of the checkpoint kinases ATM, CHK1 and CHK2, activity of the cell cycle gatekeeper kinases WEE1 and CDK1, and induction of the tumour suppressor p53 in response to stalled DNA replication. Consequently, HDAC inhibition upon replicative stress promotes mitotic catastrophe. Mechanistically, HDAC1 and HDAC2 suppress the expression of PPP2R3A/PR130, a regulatory subunit of the trimeric serine/threonine phosphatase 2 (PP2A). Genetic elimination of PR130 reveals that PR130 promotes dephosphorylation of ATM by PP2A. Moreover, the ablation of PR130 slows G1/S phase transition and increases the levels of phosphorylated CHK1, replication protein A foci and DNA damage upon replicative stress. Accordingly, stressed PR130 null cells are very susceptible to HDAC inhibition, which abrogates the S phase checkpoint, induces apoptosis and reduces the homologous recombination protein RAD51. Thus, PR130 controls cell fate decisions upon replicative stress.
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