ArticleCell discovery2021
Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis.
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Article in Cell discovery, 2021. 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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12citing papers in PubMed
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Loss of Tars induces proteostasis stress and drives HSPC exhaustion through mTORC1 activation.Acta pharmacologica Sinica · 2026Article
- RPA exhaustion activates SLFN11 to eliminate cells with heightened replication stress.Nature cell biology · 2026Article
- Unfolded protein response in bronchopulmonary dysplasia: mechanisms, pathways, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Identification of Amino Acids That Regulate Angiogenesis and Alter Pathogenesis of a Mouse Model of Choroidal Neovascularization.Nutrients · 2025Article
- GCN2-SLC7A11 axis coordinates autophagy, cell cycle and apoptosis and regulates cell growth in retinoblastoma upon arginine deprivation.Cancer & metabolism · 2024Article
- Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.Frontiers of medicine · 2024Article
- Dual targeting of glutamine and serine metabolism in acute myeloid leukemia.Frontiers in oncology · 2024Article
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors.Frontiers of medicine · 2023Article
- Unfolded protein response and angiogenesis in malignancies.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- GCN2: roles in tumour development and progression.Biochemical Society transactions · 2022Review
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Authors and funding
28 authors at 5 institutions in 2 countries.
Fan Zhang *Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qi-Yu Zeng *State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Hao Xu *Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ai-Ning Xu *Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dian-Jia LiuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ning-Zhe LiShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yi ChenShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yi JinShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chun-Hui XuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Chang-Zhou FengShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuan-Liang ZhangShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dan LiuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Na LiuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yin-Yin XieShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shan-He YuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hao YuanShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kai XueShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing-Yi ShiShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ting Xi LiuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peng-Fei XuDivision of Human Reproduction and Developmental Genetics, Women's Hospital, and Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Wei-Li ZhaoShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-6834-1616
Yi ZhouStem Cell Program, Hematology/Oncology Program at Children's Hospital Boston and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Lan WangCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qiu-Hua HuangShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-5701-0117
Zhu ChenShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sai-Juan ChenShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. sjchen@stn.sh.cn.
Xiao-Long ZhouState Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. xlzhou@sibcb.ac.cn.
Xiao-Jian SunShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine (Shanghai), Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. xjsun@sibs.ac.cn.ORCID http://orcid.org/0000-0001-8826-4614
Shanghai Jiao Tong University · CNCenter for Excellence in Molecular Cell Science · CNShanghai Institute of Nutrition and Health · CNHarvard University · USWomen's Hospital, School of Medicine, Zhejiang University · CN
Funding
National Natural Science Foundation of China (National Science Foundation of China) 81470316National Natural Science Foundation of China (National Science Foundation of China) 81670094
Abstract
The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity. Comparative transcriptome analysis of the tars-mutant and wild-type embryos with/without Gcn2- or Perk-inhibition reveals that only Gcn2-mediated AAR is activated in the tars-mutants, whereas Perk functions predominantly in normal development. Mechanistic analysis shows that, while a considerable amount of eIF2α is normally phosphorylated by Perk, the loss of Tars causes an accumulation of uncharged tRNA
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