ArticleEMBO reports2019
Checkpoint kinase 1 is essential for fetal and adult hematopoiesis.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- 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
- NFAT5 counters long-term IFN-1 responses in hematopoietic stem cells to preserve reconstitution potential.Blood advances · 2024Article
- Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy.EMBO reports · 2024Article
- Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia.Nature communications · 2024Article
- Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.Frontiers in bioengineering and biotechnology · 2024Review
- Case report: A germlineFrontiers in oncology · 2024Article
- ADAR1 links R-loop homeostasis to ATR activation in replication stress response.Nucleic acids research · 2023Article
- Chk1/2 inhibitor AZD7762 blocks the growth of preantral follicles by inducing apoptosis, suppressing proliferation, and interfering with the cell cycle in granulosa cells.Histology and histopathology · 2023Article
- The SKP2-p27 axis defines susceptibility to cell death upon CHK1 inhibition.Molecular oncology · 2022Article
- Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis.Scientific reports · 2022Article
- Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis.Cell death & disease · 2022Article
- Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents.Cancers · 2022Review
- [Oxymatrine improves renal fibrosis and inflammation in diabetic rats by modulating CHK1/2 phosphorylation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Small molecule inhibitors and a kinase-dead expressing mouse model demonstrate that the kinase activity of Chk1 is essential for mouse embryos and cancer cells.Life science alliance · 2020Article
- Regulation of stress-induced hematopoiesis.Current opinion in hematology · 2020Review
- Checkpoint kinase 1 is essential for fetal and adult hematopoiesis.EMBO reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Checkpoint kinase 1 (CHK1) is critical for S-phase fidelity and preventing premature mitotic entry in the presence of DNA damage. Tumor cells have developed a strong dependence on CHK1 for survival, and hence, this kinase has developed into a promising drug target. Chk1 deficiency in mice results in blastocyst death due to G2/M checkpoint failure showing that it is an essential gene and may be difficult to target therapeutically. Here, we show that chemical inhibition of CHK1 kills murine and human hematopoietic stem and progenitor cells (HSPCs) by the induction of BCL2-regulated apoptosis. Cell death in HSPCs is independent of p53 but requires the BH3-only proteins BIM, PUMA, and NOXA. Moreover, Chk1 is essential for definitive hematopoiesis in the embryo. Noteworthy, cell death inhibition in HSPCs cannot restore blood cell formation as HSPCs lacking CHK1 accumulate DNA damage and stop dividing. Moreover, conditional deletion of Chk1 in hematopoietic cells of adult mice selects for blood cells retaining CHK1, suggesting an essential role in maintaining functional hematopoiesis. Our findings establish a previously unrecognized role for CHK1 in establishing and maintaining hematopoiesis.
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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.