ArticleCancer research2012
Autoregulatory mechanisms of phosphorylation of checkpoint kinase 1.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Paradoxical non-catalytic kinase functions are driven by inhibitor-induced displacement of autoinhibitory domains.Molecular systems biology · 2026Article
- CHK1 inhibition rescues abnormal glycogen buildup in a Caenorhabditis elegans model for glycogen storage disease III.Communications biology · 2026Article
- REV7 associates with ATRIP and inhibits ATR kinase activity.Nucleic acids research · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Inactivation of checkpoint kinase 1 (Chk1) during parvovirus minute virus of mice (MVM) infection inhibits cellular homologous recombination repair and facilitates viral genome replication.Journal of virology · 2024Article
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Aberrant CREB1 activation in prostate cancer disrupts normal prostate luminal cell differentiation.Oncogene · 2021Article
- HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1.Cells · 2020Article
- Role for Metallothionein-3 in the Resistance of Human U87 Glioblastoma Cells to Temozolomide.ACS omega · 2020Article
- An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- 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
- Regulatory cross-talk determines the cellular levels of 53BP1 protein, a critical factor in DNA repair.The Journal of biological chemistry · 2017Article
- Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.Oxidative medicine and cellular longevity · 2017Article
- A novel Chk1-binding peptide that enhances genotoxic sensitivity through the cellular redistribution of nuclear Chk1.International journal of molecular medicine · 2016Article
- Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos.Developmental cell · 2016Article
- Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage.The Journal of biological chemistry · 2016Article
- In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2016Article
- KA1-targeted regulatory domain mutations activate Chk1 in the absence of DNA damage.Scientific reports · 2015Article
- Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage.Nature communications · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, is centrally involved in cell-cycle checkpoints and cellular response to DNA damage. Phosphorylation of Chk1 at 2 Ser/Gln (SQ) sites, Ser-317 and Ser-345, by the upstream kinase ATR is critical for checkpoint activation. However, the precise molecular mechanisms controlling Chk1 phosphorylation and subsequent checkpoint activation are not well understood. Here, we report unique autoregulatory mechanisms that control protein phosphorylation of human Chk1, as well as checkpoint activation and cell viability. Phosphorylation of Ser-317 is required, but not sufficient, for maximal phosphorylation at Ser-345. The N-terminal kinase domain of Chk1 prevents Chk1 phosphorylation at the C-terminus by ATR in the absence of DNA damage. Loss of the inhibitory effect imposed by the N-terminus causes constitutive phosphorylation of Chk1 by ATR under normal growth conditions, which in turn triggers artificial checkpoints that suppress the S-phase progression. Furthermore, two point mutations were identified that rendered Chk1 constitutively active, and expression of the constitutively active mutant form of Chk1 inhibited cancer cell proliferation. Our findings therefore reveal unique regulatory mechanisms of Chk1 phosphorylation and suggest that expression of constitutively active Chk1 may represent a novel strategy to suppress tumor growth. Cancer Res; 72(15); 3786-94. ©2012 AACR.
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Registered trials
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