ArticleeLife2022
GCN2 eIF2 kinase promotes prostate cancer by maintaining amino acid homeostasis.
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Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
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Who cites it
48 citing papers in PubMed, 52 citations in OpenAlex.
- Therapeutic rescue of pathogenic asparaginyl-tRNA synthetase alleles.Molecular therapy. Nucleic acids · 2026Article
- GCN2 in proteostasis: structural logic, signalling networks and disease.The FEBS journal · 2026Review
- Direct pharmacological targeting of asparagine synthetase to overcome resistance to L-asparaginase in ALL therapy.JCI insight · 2026Article
- Metabolic Imaging and Molecular Signatures Reveal Metabolic Phenotypes in Recurrent Glioblastoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- An inhibitor of GCN2 and the integrated stress response directly targets ZAK protein kinase to limit cytotoxicity.The Journal of biological chemistry · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Co-Targeting Nuclear Export and Translation Initiation Uncovers a Therapeutic Vulnerability in Lethal Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Intermittent Fasting and Androgen Receptor Signaling in Prostate Cancer: Metabolic Crosstalk and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma.Cell death discovery · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Inhibition of the integrated stress response rescues a histidyl-tRNA synthetase variant associated with Charcot-Marie-Tooth disease.NAR molecular medicine · 2026Article
- Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- The Dynamic UPR Rheostat Orchestrates Single-Cell Plasticity in Glioblastoma.Journal of molecular neuroscience : MN · 2025Article
- Article
- Caloric Restriction Enhances the Efficacy of Antiandrogen Therapy in Prostate Cancer by Inhibiting Androgen Receptor Translation.Cancer research · 2025Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Ricardo A CordovaDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Jagannath MisraDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Parth H AminDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Anglea J KlunkDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Nur P DamayantiIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, United States.
Kenneth R CarlsonDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Andrew J ElmendorfDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Hyeong-Geug KimDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Emily T MirekDepartment of Nutritional Sciences, Rutgers University, New Brunswick, United States.
Bennet D ElzeyDepartment of Comparative Pathology, Purdue University, West Lafayette, United States.
Marcus J MillerDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States.
X Charlie DongDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Liang ChengIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, United States.
Tracy G AnthonyDepartment of Nutritional Sciences, Rutgers University, New Brunswick, United States.
Roberto PiliJacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, United States.
Ronald C WekDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.
Kirk A StaschkeDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States.ORCID https://orcid.org/0000-0001-8722-9585
Indiana University School of MedicineIndiana University Melvin and Bren Simon Comprehensive Cancer CenterRutgers, The State University of New Jersey · USJacobs Institute · USNeurological Surgery · US
Funding
Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Sara K Quinney · 1999 to 2026
$59.3MHomeostatic Responses to Amino Acid InsufficiencyR01DK109714 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ANTHONY, TRACY G., WEK, RONALD C · 2016 to 2024
$5.4MThe pathophysiological function of PNPLA3-148M variant in alcohol-induced liver injuryR01AA028506 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI X. Charlie Dong · 2022 to 2026
$2.2MRegulation and Function of Integrated Stress ResponseR35GM136331 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI WEK, RONALD C · 2020 to 2024
$1.9MEpigenetic regulation in liver fibrosisR01DK121925 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2020 to 2023
$1.8MRole of ATG14 in the regulation of hepatic functionR01DK120689 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2020 to 2023
$1.7MRole of SIRT6 in the pancreatic beta cell agingR21AG072288 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2022 to 2023
$436kImmunomodulation by dietary protein restrictionR21CA221942 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI PILI, ROBERTO · 2018 to 2019
$381kNCI NIH HHS P30 CA082709NCI NIH HHS R21 CA221942NIAAA NIH HHS R01 AA028506NIA NIH HHS R21 AG072288NIDDK NIH HHS R01 DK109714NIDDK NIH HHS R01 DK120689NIDDK NIH HHS R01 DK121925NIGMS NIH HHS R35 GM136331
Abstract
A stress adaptation pathway termed the integrated stress response has been suggested to be active in many cancers including prostate cancer (PCa). Here, we demonstrate that the eIF2 kinase GCN2 is required for sustained growth in androgen-sensitive and castration-resistant models of PCa both in vitro and in vivo, and is active in PCa patient samples. Using RNA-seq transcriptome analysis and a CRISPR-based phenotypic screen, GCN2 was shown to regulate expression of over 60 solute-carrier (
Indexed as
eIF-2 KinaseProstatic NeoplasmsAmino AcidsAmino Acids, EssentialAndrogensAnimalsHomeostasisHumansMaleMiceMice, Inbred C57BLProtein Serine-Threonine KinasesAmino AcidsAmino Acids, EssentialAndrogensEIF2AK4 protein, humaneIF-2 KinaseProtein Serine-Threonine Kinases4F2amino acid transportcancer biologycell biologyeIF2GCN2humanISRmouseprostate cancer
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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.