ArticleMolecular cell2009
The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.
Article in Molecular cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 187 citations in OpenAlex.
- A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2013Trial
- Breast cancer genomic subtype-specific copy number alterations in metastases.Scientific reports · 2026Article
- 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
- DNA damage repair-related gene signatures delineate immune-distinct subtypes and diagnostic cues in tuberculosis.Frontiers in cellular and infection microbiology · 2026Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- 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
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in Ataxia Telangiectasia.Orphanet journal of rare diseases · 2024Article
- Development of a PROTAC Targeting Chk1.bioRxiv : the preprint server for biology · 2024Article
- BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1.Cell death discovery · 2023Article
- SCML2 contributes to tumor cell resistance to DNA damage through regulating p53 and CHK1 stability.Cell death and differentiation · 2023Article
- MYO10 regulates genome stability and cancer inflammation through mediating mitosis.Cell reports · 2023Article
- Homologous recombination suppresses transgenerational DNA end resection and chromosomal instability in fission yeast.Nucleic acids research · 2023Article
- FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy.Frontiers in oncology · 2023Review
- Adaptive exchange sustains cullin-RING ubiquitin ligase networks and proper licensing of DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.Molecular and cellular biology · 2021Article
- Systematic Analysis of FASTK Gene Family Alterations in Cancer.International journal of molecular sciences · 2021Article
- Chk1 and the Host Cell DNA Damage Response as a Potential Antiviral Target in BK Polyomavirus Infection.Viruses · 2021Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood. Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint. The protein levels of Chk1 and Fbx6 showed an inverse correlation in both cultured cancer cells and in human breast tumor tissues. Further, we show that low levels of Fbx6 and consequent impairment of replication stress-induced Chk1 degradation are associated with cancer cell resistance to the chemotherapeutic agent, camptothecin. We propose that Fbx6-dependent Chk1 degradation contributes to S phase checkpoint termination and that a defect in this mechanism might increase tumor cell resistance to certain anticancer drugs.
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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.