ArticlePLoS biology2020
Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 30 citations in OpenAlex.
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.Journal of inherited metabolic disease · 2026Review
- Repressive regulatory function of seryl-tRNA synthetase on VEGFA gene expression is impaired in renal cell carcinoma.Croatian medical journal · 2026Article
- Targeting ATM enhances radiation sensitivity of colorectal cancer by potentiating radiation-induced cell death and antitumor immunity.Journal of advanced research · 2025Article
- Altered tear fluid protein expression in persons with mild Alzheimer's disease in proteins involved in oxidative stress, protein synthesis, and energy metabolism.Journal of Alzheimer's disease : JAD · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Seryl-tRNA synthetase inhibits Wnt signaling and breast cancer progression and metastasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues.International journal of molecular sciences · 2024Review
- Emodin combined with 5-aminolevulinic acid photodynamic therapy inhibits condyloma acuminate angiogenesis by targeting SerRS.Journal of cellular and molecular medicine · 2024Article
- Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Severe pulmonary arterial hypertension in congenital sideroblastic anemia from PUS1 mutation - a case report.BMC medical genomics · 2024Article
- Protein-Protein Interactions of Seryl-tRNA Synthetases with Emphasis on Human Counterparts and Their Connection to Health and Disease.Life (Basel, Switzerland) · 2024Review
- MYC: there is more to it than cancer.Frontiers in cell and developmental biology · 2024Review
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Article
- The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease.Genes · 2022Review
- Bladder Cancer-Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP-Related Metabolic Reprogramming and SerRS O-GlcNAcylation in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The Long-Noncoding RNA TUG1 Regulates Oxygen-Induced Retinal Neovascularization in Mice via MiR-299.Investigative ophthalmology & visual science · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Hypoxia-induced angiogenesis maintains tissue oxygen supply and protects against ischemia but also enhances tumor progression and malignancy. This is mediated through activation of transcription factors like hypoxia-inducible factor 1 (HIF-1) and c-Myc, yet the impact of hypoxia on negative regulators of angiogenesis is unknown. During vascular development, seryl-tRNA synthetase (SerRS) regulates angiogenesis through a novel mechanism by counteracting c-Myc and transcriptionally repressing vascular endothelial growth factor A (VEGFA) expression. Here, we reveal that the transcriptional repressor role of SerRS is inactivated under hypoxia through phosphorylation by ataxia telangiectasia mutated (ATM) and ataxia telangiectasia mutated and RAD3-related (ATR) at Ser101 and Ser241 to attenuate its DNA binding capacity. In zebrafish, SerRSS101D/S241D, a phosphorylation-mimicry mutant, cannot suppress VEGFA expression to support normal vascular development. Moreover, expression of SerRSS101A/S241A, a phosphorylation-deficient and constitutively active mutant, prevents hypoxia-induced binding of c-Myc and HIF-1 to the VEGFA promoter, and activation of VEGFA expression. Consistently, SerRSS101A/S241A strongly inhibits normal and tumor-derived angiogenesis in mice. Therefore, we reveal a key step regulating hypoxic angiogenesis and highlight the importance of nuclear SerRS in post-developmental angiogenesis regulation in addition to vascular development. The role of nuclear SerRS in inhibiting both c-Myc and HIF-1 may provide therapeutic opportunities to correct dysregulation of angiogenesis in pathological settings.
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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.