ArticleMolecular oncology2019
SCFβ-TrCP ubiquitinates CHK1 in an AMPK-dependent manner in response to glucose deprivation.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- CHK1 inhibition rescues abnormal glycogen buildup in a Caenorhabditis elegans model for glycogen storage disease III.Communications biology · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- DEPTOR suppresses lymphomagenesis by promoting EGFR degradation via HUWE1 E3 ligase.Cell death and differentiation · 2025Article
- Exosomes derived from hUC-MSCs exhibit ameliorative efficacy upon previous cesarean scar defect via orchestrating β-TrCP/CHK1 axis.Scientific reports · 2025Article
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1.Cell death discovery · 2023Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
- P90 ribosomal S6 kinase confers cancer cell survival by mediating checkpoint kinase 1 degradation in response to glucose stress.Cancer science · 2022Article
- CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment.Cell reports · 2021Article
- Genetic fusions favor tumorigenesis through degron loss in oncogenes.Nature communications · 2021Article
- New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.International journal of molecular sciences · 2021Review
- DEPTOR stabilizes ErbB2 to promote the proliferation and survival of ErbB2-positive breast cancer cells.Theranostics · 2021Article
- Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is required for CHK1 activation.Journal of hematology & oncology · 2020Article
- SCFOncogenesis · 2020Article
- Basal CHK1 activity safeguards its stability to maintain intrinsic S-phase checkpoint functions.The Journal of cell biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
The ATR/CHK1 pathway is a key effector of cellular response to DNA damage and therefore is a critical regulator of genomic stability. While the ATR/CHK1 pathway is often inactivated by mutations, CHK1 itself is rarely mutated in human cancers. Thus, cellular levels of CHK1 likely play a key role in the maintenance of genomic stability and preventing tumorigenesis. Glucose deprivation is observed in many solid tumors due to high glycolytic rates of cancer cells and insufficient vascularization, yet cancer cells have devised mechanisms to survive in conditions of low glucose. Although CHK1 degradation through the ubiquitin-proteasome pathway following glucose deprivation has been previously reported, the detailed molecular mechanisms remain elusive. Here, we show that CHK1 is ubiquitinated and degraded upon glucose deprivation by the Skp1-Cullin-F-box (β-TrCP) E3 ubiquitin ligase. Specifically, CHK1 contains a β-TrCP recognizable degron domain, which is phosphorylated by AMPK in response to glucose deprivation, allowing for β-TrCP to recognize CHK1 for subsequent ubiquitination and degradation. Our results provide a novel mechanism by which glucose metabolism regulates a DNA damage effector, and imply that glucose deprivation, which is often found in solid tumor microenvironments, may enhance mutagenesis, clonal expansion, and tumor progression by triggering CHK1 degradation.
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