ArticleProceedings of the National Academy of Sciences of the United States of America2013
Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- FBXW7-mediated CHK2 regulation modulates DNA damage response and cellular stability in Huntington's disease.Cell death discovery · 2025Article
- Decoding sexually dimorphic proteomic landscapes in the context of aging and mortality.Communications medicine · 2025Article
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Small molecule targeting of the p38/Mk2 stress signaling pathways to improve cancer treatment.BMC cancer · 2023Article
- MAD2L2 promotes replication fork protection and recovery in a shieldin-independent and REV3L-dependent manner.Nature communications · 2022Article
- The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress.Science translational medicine · 2021Article
- γδ T cell IFNγ production is directly subverted by Yersinia pseudotuberculosis outer protein YopJ in mice and humans.PLoS pathogens · 2021Article
- Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways.Biomolecules · 2021Review
- SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.The EMBO journal · 2021Article
- MK2 degradation as a sensor of signal intensity that controls stress-induced cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Chemotherapeutic drugs: Cell death- and resistance-related signaling pathways. Are they really as smart as the tumor cells?Translational oncology · 2021Review
- Combined inhibition of Aurora-A and ATR kinase results in regression ofNature cancer · 2021Article
- The integrated stress response induces R-loops and hinders replication fork progression.Cell death & disease · 2020Article
- Nitrogen starvation reveals the mitotic potential of mutants in the S/MAPK pathways.Nature communications · 2020Article
- Article
- Targeting gallbladder cancer: a pathway based perspective.Molecular biology reports · 2020Review
- Modeling of Cisplatin-Induced Signaling Dynamics in Triple-Negative Breast Cancer Cells Reveals Mediators of Sensitivity.Cell reports · 2019Article
- Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing.The EMBO journal · 2019Article
- Screening common signaling pathways associated with drug resistance in non-small cell lung cancer via gene expression profile analysis.Cancer medicine · 2019Article
- Efficient disruption of bcr-abl gene by CRISPR RNA-guided FokI nucleases depresses the oncogenesis of chronic myeloid leukemia cells.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (γH2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation. Moreover, MK2 activity was required for damage response, accumulation of ssDNA, and decreased survival when cells were treated with the nucleoside analogue gemcitabine or when the checkpoint kinase Chk1 was antagonized. By using DNA fiber assays, we found that MK2 inhibition or knockdown rescued DNA replication impaired by gemcitabine or by Chk1 inhibition. This rescue strictly depended on translesion DNA polymerases. In conclusion, instead of being an unavoidable consequence of DNA damage, alterations of replication speed and origin firing depend on MK2-mediated signaling.
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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.