ArticleOncogene2025
ROS-ATM-CHK2 axis stabilizes HIF-1α and promotes tumor angiogenesis in hypoxic microenvironment.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Integrative Genomic and Transcriptomic Insights into High-Altitude Adaptation in Changthangi Goats.Applied biochemistry and biotechnology · 2026Article
- Integrated transcriptomics identifies HIF1A and GSTP1 as biomarkers for cutaneous squamous cell carcinoma.Translational cancer research · 2026Article
- The Mechanism of MgInternational journal of molecular sciences · 2026Article
- HIF-1α mediated placental ischemic signaling in the development of early-onset preeclampsia.Redox biology · 2026Review
- Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.Journal of molecular cell biology · 2026Review
- Advances in the Research of Hypoxia-Inducible Factor-1Alpha and Plasminogen Activator Inhibitor-1 in Vascular-Related Diseases.Journal of clinical medicine research · 2026Review
- Punicalin Modulates Angiogenesis and Tumor Microenvironment-Related Processes in Triple-Negative Breast Cancer and Endothelial Cells.International journal of molecular sciences · 2026Article
- Spatial immune niche remodeling of the neutrophil-macrophage axis inchronic liver disease.Frontiers in cell and developmental biology · 2026Review
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Immuno-oncological interactions between meningeal lymphatics and glioblastoma: from mechanisms to therapies.Theranostics · 2025Review
- Characterization of hypoxia-related molecular clusters and prognostic riskScore for glioma.Frontiers in oncology · 2025Article
- Radiation-induced alterations in the cancer microenvironment (Review).Medicine internationalReview
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Hypoxia is an established hallmark of tumorigenesis. HIF-1α activation may be the prime driver of adaptive regulation of tumor cells reacting to hypoxic conditions of the tumor microenvironment. Here, we report a novel regulatory mechanism in charge of the fundamental stability of HIF-1α in solid tumor. Under hypoxic conditions, the checkpoint kinase CHK2 binds to HIF-1α and inhibits its ubiquitination, which is highly likely due to phosphorylation of a threonine residue (Thr645), a formerly uncharacterized site within the inhibitory domain. Meanwhile, HIF-1α phosphorylation induced by CHK2 promotes complex formation between HIF-1-α and the deubiquitination enzyme USP7, increasing stability under hypoxic conditions. This novel modification of the crosstalk between phosphorylation and ubiquitination of HIF-1α mediated by CHK2 enriches the post-translational modification spectrum of HIF-1α, thus offering novel insights into potential anti-angiogenesis therapies.
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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.