ArticleMolecular biology of the cell2004
Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- CHK1 is an integral regulator of DNA replication in human cells.Cell death & disease · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- FNDC5/irisin mitigates the cardiotoxic impacts of cancer chemotherapeutics by modulating ROS-dependent and -independent mechanisms.Redox biology · 2025Article
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- Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1.The FEBS journal · 2020Article
- SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication.Nature communications · 2019Article
- Proteome-wide analysis of chaperone-mediated autophagy targeting motifs.PLoS biology · 2019Article
- A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells.Oncotarget · 2018Article
- Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain.The Journal of biological chemistry · 2017Article
- A novel Chk1-binding peptide that enhances genotoxic sensitivity through the cellular redistribution of nuclear Chk1.International journal of molecular medicine · 2016Article
- Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage.The Journal of biological chemistry · 2016Article
- KA1-targeted regulatory domain mutations activate Chk1 in the absence of DNA damage.Scientific reports · 2015Article
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- Loss of compensatory pro-survival and anti-apoptotic modulator, IKKε, sensitizes ovarian cancer cells to CHEK1 loss through an increased level of p21.Oncotarget · 2014Article
- Src family kinases promote silencing of ATR-Chk1 signaling in termination of DNA damage checkpoint.The Journal of biological chemistry · 2014Article
- Roles of Chk1 in cell biology and cancer therapy.International journal of cancer · 2014Review
- Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition.Cell cycle (Georgetown, Tex.) · 2014Article
- Checkpoint kinase 1 in DNA damage response and cell cycle regulation.Cellular and molecular life sciences : CMLS · 2013Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The checkpoint kinase Chk1 undergoes ATR-mediated phosphorylation and activation in response to unreplicated DNA, but the precise mechanism of Chk1 activation is not known. In this study, we have analyzed the domain structure of Xenopus Chk1 and explored the mechanism of its activation by ATR-mediated phosphorylation. We show that the C-terminal region of Xenopus Chk1 contains an autoinhibitory region (AIR), which largely overlaps with a bipartite, unusually long ( approximately 85-amino acid) nuclear localization signal. When coexpressed in oocytes or embryos, the AIR can interact with and inhibit the kinase domain of Chk1, but not full-length Chk1, suggesting an autoinhibitory intramolecular interaction in the Chk1 molecule. If linked with the preceding ATR phosphorylation domain that has either phospho-mimic mutation or genuine phosphorylation, however, the AIR can no longer interact with or inhibit the kinase domain, suggesting a conformational change of the AIR by ATR-mediated phosphorylation. Even in full-length Chk1, such phospho-mimic mutation can interfere with the autoinhibitory intramolecular interaction, but only if this interaction is somewhat weakened by an additional mutation in the AIR. These results provide significant insights into the mechanism of Chk1 activation at the DNA replication checkpoint.
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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.