ArticleThe Journal of biological chemistry2017
Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- 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
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.EMBO reports · 2024Article
- DEAD box RNA helicases are pervasive protein kinase interactors and activators.Genome research · 2024Article
- Case report: A germlineFrontiers in oncology · 2024Article
- Spatiotemporal regulation of MELK during mitosis.Frontiers in cell and developmental biology · 2024Article
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- Maternal heterozygous mutation in CHEK1 leads to mitotic arrest in human zygotes.Protein & cell · 2022Article
- Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein.Structure (London, England : 1993) · 2021Article
- Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1.The FEBS journal · 2020Article
- Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins.Advances in experimental medicine and biology · 2019Review
- Chk1 KA1 domain auto-phosphorylation stimulates biological activity and is linked to rapid proteasomal degradation.Scientific reports · 2018Article
- Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.Structure (London, England : 1993) · 2018Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Precise control of the cell cycle allows for timely repair of genetic material prior to replication. One factor intimately involved in this process is checkpoint kinase 1 (Chk1), a DNA damage repair inducing Ser/Thr protein kinase that contains an N-terminal kinase domain and a C-terminal regulatory region consisting of a ∼100-residue linker followed by a putative kinase-associated 1 (KA1) domain. We report the crystal structure of the human Chk1 KA1 domain, demonstrating striking structural homology with other sequentially diverse KA1 domains. Separately purified Chk1 kinase and KA1 domains are intimately associated in solution, which results in inhibition of Chk1 kinase activity. Using truncation mutants and site-directed mutagenesis, we define the inhibitory face of the KA1 domain as a series of basic residues residing on two conserved regions of the primary structure. These findings point to KA1-mediated intramolecular autoinhibition as a key regulatory mechanism of human Chk1, and provide new therapeutic possibilities with which to attack this validated oncology target with small molecules.
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