ArticleCell cycle (Georgetown, Tex.)2012
The stress-activated protein kinases p38α/β and JNK1/2 cooperate with Chk1 to inhibit mitotic entry upon DNA replication arrest.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology.International journal of molecular sciences · 2025Review
- The PIN1-p38-CtIP signalling axis protects stalled replication forks from deleterious degradation.Nucleic acids research · 2025Article
- Roles of p38 MAPK signalling in intervertebral disc degeneration.Cell proliferation · 2023Review
- Kullback-Leibler Divergence of an Open-Queuing Network of a Cell-Signal-Transduction Cascade.Entropy (Basel, Switzerland) · 2023Article
- Claspin-Dependent and -Independent Chk1 Activation by a Panel of Biological Stresses.Biomolecules · 2023Article
- Epidermal growth factor receptor cascade prioritizes the maximization of signal transduction.Scientific reports · 2022Article
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- Plasma membrane proteoglycans syndecan-2 and syndecan-4 engage with EGFR and RON kinase to sustain carcinoma cell cycle progression.The Journal of biological chemistry · 2022Article
- RAD51 is a druggable target that sustains replication fork progression upon DNA replication stress.PloS one · 2022Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- p38β and Cancer: The Beginning of the Road.International journal of molecular sciences · 2020Review
- DNA damage response manages cell cycle restriction of senile multipotent mesenchymal stromal cells.Molecular biology reports · 2020Review
- MASTL overexpression promotes chromosome instability and metastasis in breast cancer.Oncogene · 2018Article
- Article
- miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.Nature communications · 2016Article
- p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity.Nature medicine · 2016Article
- New origin firing is inhibited by APC/CCdh1 activation in S-phase after severe replication stress.Nucleic acids research · 2016Article
- Article
- Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBN(p70) protein undergo p38/MK2-dependent premature senescence.Biogerontology · 2015Article
- Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation.Journal of leukocyte biology · 2013Review
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accurate DNA replication is crucial for the maintenance of genome integrity. To this aim, cells have evolved complex surveillance mechanisms to prevent mitotic entry in the presence of partially replicated DNA. ATR and Chk1 are key elements in the signal transduction pathways of DNA replication checkpoint; however, other kinases also make significant contributions. We show here that the stress kinases p38 and JNK are activated when DNA replication is blocked, and that their activity allows S/M, but not G 2/M, checkpoint maintenance when Chk1 is inhibited. Activation of both kinases by DNA replication inhibition is not mediated by the caffeine-sensitive kinases ATR or ATM. Phosphorylation of MKK3/6 and MKK4, p38 and JNK upstream kinases was also observed upon DNA replication inhibition. Using a genetic approach, we dissected the p38 pathway and showed that both p38α and p38β isoforms collaborate to inhibit mitotic entry. We further defined MKK3/6 and MK2/3 as the key upstream and downstream elements in the p38 signaling cascade after replication arrest. Accordingly, we found that the stress signaling pathways collaborate with Chk1 to keep cyclin B1/Cdk1 complexes inactive when DNA replication is inhibited, thereby preventing cell cycle progression when DNA replication is stalled. Our results show a complex response to replication stress, where multiple pathways are activated and fulfill overlapping roles to prevent mitotic entry with unreplicated DNA.
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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.