Affinage

GLS

Glutaminase kidney isoform, mitochondrial · UniProt O94925

Length
669 aa
Mass
73.5 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLS (kidney-type glutaminase) is a mitochondrial enzyme that initiates glutaminolysis, converting glutamine to glutamate to feed the TCA cycle, redox defense, and biosynthesis; its splice isoforms KGA and GAC are mitochondrially localized in neurons, astrocytes, and tumor cells (PMID:25297978, PMID:32727118), and the GAC variant in particular is required for cancer cell proliferation, with growth defects upon knockdown rescued by downstream glutaminolysis metabolites (PMID:22892846). Catalytic output is tuned by post-translational regulation: under oxidative stress, p38-MAPK-phosphorylated SUCLA2 dissociates from GLS, enabling K311 succinylation, oligomerization, and elevated activity that drives NADPH and glutathione production (PMID:33991485), while glutamine deprivation triggers conversion of dimeric GLS into hyperactive self-assembled filaments that further deplete glutamine and provoke ROS-induced apoptosis rescued by asparagine (PMID:35381197). GLS protein abundance is set by competing ubiquitin-proteasome inputs through APC/C-CDH1, promoted by selenite and by PPARγ agonists acting via the CDK1-APC/C-Cdh1 axis (PMID:27902968, PMID:34267342), and by SIRT4-, SIRT5-, USP6-, and YTHDF1-dependent control of stability and translation (PMID:37541633, PMID:35091542, PMID:33614908). Transcriptionally, GLS1 is induced by c-Myc, which binds the GLS1 promoter, and GLS1 reciprocally stabilizes c-Myc through a USP1-dependent mechanism, forming a feed-forward loop that drives cancer cell invasion (PMID:39024547); additional inputs include c-Jun downstream of MALT1 in Th17/psoriasis settings and ARID1A loss releasing SWI/SNF repression of the locus (PMID:32831293, PMID:34085048). In the nervous system, a de novo gain-of-function S482C variant causes enzyme hyperactivity, glutamate excess, infantile cataract and developmental delay (PMID:30239721), whereas complete GLS loss causes autosomal recessive spastic ataxia with optic atrophy, establishing GLS as essential for glutamate homeostasis (PMID:29468182).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2012 Medium

    Established that a specific GLS1 splice isoform, GAC, is the metabolically critical product driving cancer cell growth, framing glutaminase as a dependency rather than a housekeeping enzyme.

    Evidence isoform-specific siRNA knockdown with downstream metabolite rescue in NSCLC cells

    PMID:22892846

    Open questions at the time
    • Does not resolve which downstream metabolite is rate-limiting
    • Single cell-line context
    • No in vivo validation
  2. 2014 Medium

    Resolved the subcellular distribution of GLS, confirming mitochondrial localization of KGA/GAC in neurons and astrocytes and distinguishing it from nuclear-capable GLS2.

    Evidence isoform-specific immunocytochemistry, confocal microscopy and in situ activity staining in rat and human brain

    PMID:25297978

    Open questions at the time
    • Does not address regulation of localization
    • Functional consequence of compartmentalization not tested
  3. 2018 Medium

    Demonstrated that complete loss of GLS causes a human neurological disease, establishing GLS as essential for normal nervous system function.

    Evidence homozygosity mapping and whole-genome sequencing of a family with spastic ataxia and confirmed absence of GLS expression

    PMID:29468182

    Open questions at the time
    • Single family report
    • Mechanism linking glutaminase loss to optic atrophy/spasticity not defined
  4. 2019 High

    Showed that a gain-of-function point mutation in the catalytic environment produces enzyme hyperactivity and glutamate excess, defining the opposite disease pole from loss-of-function and pinpointing a regulatory residue.

    Evidence patient fibroblast biochemistry, zebrafish expression model with GLS-inhibitor rescue, and MR spectroscopy

    PMID:30239721

    Open questions at the time
    • Structural basis inferred rather than crystallographically resolved
    • Single de novo variant
  5. 2021 High

    Defined a stress-responsive post-translational switch in which SUCLA2 release permits K311 succinylation, oligomerization, and activation of GLS to fuel antioxidant output.

    Evidence reciprocal Co-IP, phospho/succinyl-site mutagenesis, in vitro activity assays, and mouse xenografts

    PMID:33991485

    Open questions at the time
    • Identity of the succinyltransferase not established
    • Relationship between succinylation and filament assembly unclear
  6. 2022 High

    Established that glutamine deprivation drives GLS dimer-to-filament conversion as a self-amplifying hyperactive state with cell-fate consequences, linking enzyme assembly to apoptosis.

    Evidence biochemical filament reconstitution, K320A/S482C mutants, asparagine rescue and xenograft tumor models

    PMID:35381197

    Open questions at the time
    • High-resolution filament architecture not provided
    • Physiological triggers beyond glutamine deprivation untested
  7. 2020 High

    Connected upstream signaling to GLS1 transcription and downstream chromatin output, showing MALT1/c-Jun-driven GLS1 expression supports Th17 differentiation via histone acetylation at Il17a.

    Evidence ChIP for c-Jun promoter binding and H3 acetylation, protease and GLS1 inhibition in psoriasis mouse models

    PMID:32831293

    Open questions at the time
    • Does not quantify metabolite flux to acetyl-CoA in vivo
    • Generality beyond skin inflammation unknown
  8. 2021 High

    Identified ARID1A/SWI/SNF as a chromatin repressor of GLS1, creating a synthetic-lethal vulnerability to glutaminase inhibition in ARID1A-mutant cancer.

    Evidence ARID1A genetic inactivation, ChIP, 13C metabolic tracing and CB-839 in orthotopic and PDX models

    PMID:34085048

    Open questions at the time
    • Direct SWI/SNF occupancy dynamics over time not resolved
    • Restricted to ovarian clear cell context
  9. 2024 High

    Demonstrated a reciprocal GLS1-c-Myc feedback loop in which c-Myc transcribes GLS1 and GLS1 stabilizes c-Myc via USP1, coupling glutamine metabolism to oncogenic invasion.

    Evidence genetic and CB-839 perturbation, ChIP, ubiquitination assays and orthotopic mouse model

    PMID:39024547

    Open questions at the time
    • Mechanism by which GLS1 controls USP1 not defined
    • Whether the loop operates outside the studied cancers untested
  10. 2023 Medium

    Mapped sirtuin- and deubiquitinase-based control of GLS1 stability, showing SIRT4 antagonizes SIRT5 stabilization to limit glutaminolysis and α-ketoglutarate-driven ECM transcription.

    Evidence Co-IP of SIRT4/SIRT5/GLS1, activity assays and in vivo intestinal fibrosis models

    PMID:37541633

    Open questions at the time
    • Direct enzymatic modification of GLS1 by these sirtuins not shown
    • Single disease model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers — succinylation, filament assembly, APC/C-CDH1 degradation, and transcriptional feedback — are integrated into a single quantitative control scheme for GLS activity in normal versus diseased tissue remains unresolved.
  • No unified model linking PTM state to assembly state to flux
  • Tissue-specific regulatory hierarchy undefined
  • Structural mechanism of catalytic-site mutations and filament gating not crystallographically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CDH1MYCNFS1SIRT4SIRT5SUCLA2USP6YTHDF1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 The GLS1 splice variant GAC (glutaminase C) is essential for non-small cell lung cancer cell growth. Transient knockdown of GLS1 splice variants showed that loss of GAC had the most detrimental effect on cancer cell growth, and decreased growth could be rescued by exogenous addition of downstream glutaminolysis metabolites. siRNA knockdown of GLS1 splice variants, metabolite rescue assay Cancer biology & therapy Medium 22892846
2021 Upon oxidative stress, SUCLA2 (phosphorylated by p38 MAPK at S79) dissociates from GLS, resulting in enhanced GLS K311 succinylation, oligomerization, and enzymatic activity. Activated GLS increases glutaminolysis and production of NADPH and glutathione to counteract oxidative stress. SUCLA2 thus acts as a negative regulator of GLS succinylation. Co-IP, phosphorylation/succinylation site mutagenesis, in vitro enzymatic activity assay, mouse xenograft model Molecular cell High 33991485
2022 Glutamine deprivation causes GLS1 to convert from a dimer to a self-assembled filamentous polymer with enhanced catalytic activity (lower Km). Filamentous GLS1 further depletes intracellular glutamine, leading to inadequate asparagine synthesis and ROS-induced apoptosis. Asparagine supplementation rescues this apoptosis. Constitutively active filamentous mutants K320A and S482C suppress tumor growth in xenograft models. Structural/biochemical characterization of GLS1 filaments, mutagenesis (K320A, S482C), metabolite rescue (asparagine), xenograft tumor models Molecular cell High 35381197
2019 A gain-of-function de novo variant Ser482Cys in GLS causes hyperactivity of the enzyme, likely by improving the electrostatic environment of the catalytic site. This leads to increased glutamate and decreased glutamine in urine, fibroblasts, and brain, resulting in infantile cataract and profound developmental delay. Inhibition of GLS alleviated cataract in zebrafish expressing Ser482Cys-GLS. Functional analysis of patient-derived fibroblasts, zebrafish expression model, GLS inhibitor rescue, MR spectroscopy, protein sequence conservation analysis Human molecular genetics High 30239721
2018 GLS loss-of-function (complete knockout due to a homozygous copy number variant) causes autosomal recessive spastic ataxia with optic atrophy in humans, establishing that GLS is required for normal neurological function. Homozygosity mapping, whole-genome sequencing, confirmation of complete absence of GLS expression Annals of clinical and translational neurology Medium 29468182
2014 The GLS isoform (KGA/GAC) is localized to mitochondria in both neurons and astrocytes, while GLS2 appears in two locations: mitochondria and nucleus. Astrocytic glutaminase proteins encoded by both GLS and GLS2 possess enzymatic activity demonstrated by in situ activity staining. Isoform-specific immunocytochemistry, confocal microscopy, quantitative RT-PCR, in situ enzymatic activity staining in rat and human brain tissue Glia Medium 25297978
2021 ARID1A inactivation upregulates GLS1 expression by releasing SWI/SNF-mediated repression of the GLS1 gene, increasing glutamine utilization through the TCA cycle to support aspartate synthesis. Pharmacological GLS1 inhibition (CB-839) selectively suppresses growth of ARID1A-mutant ovarian clear cell carcinoma in orthotopic and patient-derived xenograft models. Genetic ARID1A inactivation, ChIP (SWI/SNF binding at GLS1 locus), metabolomics (13C tracing), CB-839 treatment in xenograft models Nature cancer High 34085048
2020 MALT1 protease stabilizes c-Jun by cleavage, and c-Jun directly binds the GLS1 promoter to upregulate GLS1 expression. GLS1-mediated glutaminolysis promotes Th17 differentiation through enhancement of histone H3 acetylation at the Il17a promoter. IL-17A in turn enhances GLS1 expression via the MALT1/c-Jun pathway in keratinocytes. ChIP assay (c-Jun binding to GLS1 promoter and H3 acetylation at Il17a), protease inhibition, GLS1 inhibition in psoriasis mouse models The Journal of clinical investigation High 32831293
2017 Selenite promotes GLS1 protein degradation via the APC/C-CDH1 ubiquitin-proteasome pathway. Selenite promotes association of APC/C-CDH1 with GLS1, leading to GLS1 ubiquitination and degradation, which is related to induction of PTEN expression. Co-immunoprecipitation, ubiquitination assay, western blot, GLS1 activity assay Oncotarget Medium 27902968
2021 PPARγ agonists repress GLS1 expression through the CDK1-APC/C-Cdh1 signaling axis, leading to ubiquitin-proteasomal degradation of GLS1. This inhibits glutaminolysis and Th17 differentiation, reducing 2-HG production and H3K4me3 modification at the il-17 gene locus. Western blot, flow cytometry, ChIP (H3K4me3), GLS1 overexpression rescue, mouse colitis/asthma models Acta pharmacologica Sinica Medium 34267342
2023 SIRT4 facilitates GLS1 degradation by hindering SIRT5's stabilizing interaction with GLS1, thereby reducing glutaminolysis and alleviating intestinal fibrosis. α-ketoglutarate produced by GLS1 acts as a key metabolite mediating ECM transcription via KDM6. Co-immunoprecipitation (SIRT4/SIRT5/GLS1 interaction), western blot, GLS1 activity assay, in vivo intestinal fibrosis models Matrix biology Medium 37541633
2019 GLS1 overexpression increases phospho-AKT, phospho-GSK3β, and cyclinD1 expression in hepatocellular carcinoma cells without affecting total AKT or GSK3β, indicating GLS1 promotes proliferation via the AKT/GSK3β/CyclinD1 pathway. GLS1 overexpression/knockdown, western blot for pathway components, cell proliferation assay, GLS1 inhibitor (compound 968) treatment Experimental cell research Low 31054856
2022 USP6 deubiquitylase increases GLS1 ubiquitination to decrease GLS protein stability, and this process is regulated by miR-146a-5p. hucMSC exosomes deliver miR-146a-5p to suppress USP6, thereby reducing GLS1 ubiquitination and increasing GLS1 protein levels. Co-immunoprecipitation, ubiquitination assay, western blot, miRNA overexpression/inhibition Cell death & disease Medium 35091542
2020 c-Myc upregulates KGA and GAC (GLS1 isoforms) protein levels in EBV-infected cells, which in turn elevate intracellular glutamate and activate mitochondrial glutaminolysis. GLS1 isoforms are mitochondrially localized in EBV-infected cells. Western blot, GLS1 isoform inhibitors, mitochondrial fractionation/localization, cell proliferation assay Viruses Low 32727118
2024 GLS1 disruption (genetic depletion or CB-839 treatment) reduces c-Myc protein stability via a ubiquitin-specific peptidase 1 (USP1)-dependent ubiquitin-proteasome pathway. Conversely, c-Myc directly binds to the GLS1 promoter and upregulates GLS1 transcription, forming a positive feedback loop. The GLS1-c-Myc axis promotes acetyl-CoA carboxylase-dependent Slug acetylation, driving cancer cell invasion. Genetic GLS1 depletion, CB-839 treatment, ChIP (c-Myc binding to GLS1 promoter), ubiquitination assay, orthotopic mouse model Cancer research High 39024547
2022 SMYD2 methylates c-Myc to increase its protein stability (reducing K48-linked polyubiquitination), which upregulates GLS1 expression. SMYD2 depletion destabilizes c-Myc and reduces GLS1 levels and glutamine metabolism in HCC cells. Co-IP, western blot for ubiquitination, GLS1 expression analysis after SMYD2 knockdown/overexpression, in vivo xenograft Cells Medium 36611819
2020 NUDT21 downregulation (driven by hypoxia via HIF-1α) alters GLS1 pre-mRNA splicing, shifting expression from KGA to GAC isoforms. This links hypoxic tumor environments to aberrant glutamine metabolism. NUDT21 shRNA knockdown, RT-PCR for GLS1 splice variants, HIF-1α modulation, xenograft model Biochemical and biophysical research communications Medium 32228887
2021 YAP1 protects vascular smooth muscle cells against ferroptosis by regulating GLS1 expression to promote synthesis of glutamate and glutathione. YAP1 knockdown decreases GLS1 expression and increases ferroptosis susceptibility. YAP1 knockdown/overexpression, western blot for GLS1, glutamate/GSH measurement, ferroptosis assays in VSMCs FASEB journal Low 39091212
2021 YTHDF1 binds to the 3' UTR of GLS1 mRNA (validated by RNA immunoprecipitation) and promotes GLS1 protein synthesis. YTHDF1-mediated upregulation of GLS1 drives glutamine metabolism and cisplatin resistance in colorectal cancer cells. RNA immunoprecipitation (RIP) assay, YTHDF1 overexpression/knockdown, western blot for GLS1, in vivo xenograft Molecular therapy oncolytics Medium 33614908
2024 GLS1 interacts with NFS1 (iron-sulfur cluster assembly enzyme) and regulates Fe2+ homeostasis. GLS1-driven glutamine metabolism facilitates acetyl-CoA production, which promotes histone acetylation of NFS1, establishing a link between GLS1 activity and iron homeostasis in nucleus pulposus cells. Co-immunoprecipitation (GLS1-NFS1 interaction), GLS1 overexpression, metabolite measurement, histone acetylation assay Free radical biology & medicine Low 39710108
2019 GLS1 knockdown in prostate cancer cells suppresses the Wnt/β-catenin pathway (decreased cyclinD1 and Bcl-2, increased Bax), inducing apoptosis and cell cycle arrest. GLS1 siRNA knockdown, western blot for Wnt/β-catenin pathway components, apoptosis and cell cycle assays Bioscience reports Low 31196962

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Science advances 604 28875174
2007 Gac/Rsm signal transduction pathway of gamma-proteobacteria: from RNA recognition to regulation of social behaviour. Molecular microbiology 420 18047567
1998 Involvement of receptor-like protein tyrosine phosphatase zeta/RPTPbeta and its ligand pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) in neuronal migration. The Journal of cell biology 203 9660874
2012 Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth. Cancer biology & therapy 192 22892846
2021 SUCLA2-coupled regulation of GLS succinylation and activity counteracts oxidative stress in tumor cells. Molecular cell 166 33991485
2015 MiRNA-192 [corrected] and miRNA-204 Directly Suppress lncRNA HOTTIP and Interrupt GLS1-Mediated Glutaminolysis in Hepatocellular Carcinoma. PLoS genetics 146 26710269
2021 GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy. Theranostics 144 34335968
2000 Heparin-binding proteins HB-GAM (pleiotrophin) and amphoterin in the regulation of cell motility. Matrix biology : journal of the International Society for Matrix Biology 130 10980414
1991 Lambda Gam protein inhibits the helicase and chi-stimulated recombination activities of Escherichia coli RecBCD enzyme. Journal of bacteriology 122 1653221
2021 Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism. Molecular therapy oncolytics 113 33614908
2021 Targeting glutamine dependence through GLS1 inhibition suppresses ARID1A-inactivated clear cell ovarian carcinoma. Nature cancer 108 34085048
2020 GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis. The Journal of clinical investigation 101 32831293
2018 Nutrient Stress-Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression. Cancer research 101 30563888
1994 Expression of HB-GAM (heparin-binding growth-associated molecules) in the pathways of developing axonal processes in vivo and neurite outgrowth in vitro induced by HB-GAM. Brain research. Developmental brain research 100 7955315
1997 HB-GAM (heparin-binding growth-associated molecule) and heparin-type glycans in the development and plasticity of neuron-target contacts. Progress in neurobiology 91 9185236
2023 m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming. Cell death & disease 83 37582794
2020 Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma. Cancer & metabolism 83 32158544
2013 Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells. Journal of molecular medicine (Berlin, Germany) 83 24276018
2019 Multiomics Analysis Reveals that GLS and GLS2 Differentially Modulate the Clinical Outcomes of Cancer. Journal of clinical medicine 77 30871151
2021 Targeting GLS1 to cancer therapy through glutamine metabolism. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 73 34023970
2013 The Gac/Rsm and cyclic-di-GMP signalling networks coordinately regulate iron uptake in Pseudomonas aeruginosa. Environmental microbiology 70 23796404
2022 Identification of GLS as a cuproptosis-related diagnosis gene in acute myocardial infarction. Frontiers in cardiovascular medicine 69 36440046
2022 Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis. Molecular cell 68 35381197
2013 Effect of GAC pre-treatment and disinfectant on microbial community structure and opportunistic pathogen occurrence. Water research 65 23906775
2019 Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer. Bioscience reports 57 31196962
2019 GLS1 promotes proliferation in hepatocellular carcinoma cells via AKT/GSK3β/CyclinD1 pathway. Experimental cell research 56 31054856
2003 The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku. EMBO reports 55 12524520
2020 Biochar and GAC intensify anaerobic phenol degradation via distinctive adsorption and conductive properties. Journal of hazardous materials 54 33092879
2007 The crystal structure of lambda-Gam protein suggests a model for RecBCD inhibition. Journal of molecular biology 54 17544443
2021 The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists. Theranostics 53 33754076
2021 Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin. Nature methods 52 33963348
2014 Expression of Gls and Gls2 glutaminase isoforms in astrocytes. Glia 50 25297978
2013 Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 46 24096582
2022 Metabolomics-assisted discovery of a new anticancer GLS-1 inhibitor chemotype from a nortopsentin-inspired library: From phenotype screening to target identification. European journal of medicinal chemistry 44 35286926
2021 GLS1 depletion inhibited colorectal cancer proliferation and migration via redox/Nrf2/autophagy-dependent pathway. Archives of biochemistry and biophysics 44 34119480
2008 The gac-gene cluster for the production of acarbose from Streptomyces glaucescens GLA.O: identification, isolation and characterization. Journal of biotechnology 44 19059289
2017 Knockdown of PKM2 and GLS1 expression can significantly reverse oxaliplatin-resistance in colorectal cancer cells. Oncotarget 43 28498807
1995 Co-expression of heparin-binding growth-associated molecule (HB-GAM) and N-syndecan (syndecan-3) in developing rat brain. Neuroscience letters 42 7659286
2015 miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells. Biochemical and biophysical research communications 40 25824045
2007 The lambda Gam protein inhibits RecBCD binding to dsDNA ends. Journal of molecular biology 40 17583735
1999 Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain. The European journal of neuroscience 40 10051750
2021 Bergenin, a PPARγ agonist, inhibits Th17 differentiation and subsequent neutrophilic asthma by preventing GLS1-dependent glutaminolysis. Acta pharmacologica Sinica 39 34267342
2019 miR-145 inhibits glutamine metabolism through c-myc/GLS1 pathways in ovarian cancer cells. Cell biology international 39 31115975
2023 Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C. Nature methods 38 37336949
1993 In vivo studies on the interaction of RecBCD enzyme and lambda Gam protein. Journal of bacteriology 37 8335632
2019 GLS hyperactivity causes glutamate excess, infantile cataract and profound developmental delay. Human molecular genetics 36 30239721
2022 HucMSC exosomes promoted imatinib-induced apoptosis in K562-R cells via a miR-145a-5p/USP6/GLS1 axis. Cell death & disease 32 35091542
2021 SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis. Frontiers in oncology 32 34490096
2005 A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression. Oncogene 32 15856007
2009 GLS-1, a novel P granule component, modulates a network of conserved RNA regulators to influence germ cell fate decisions. PLoS genetics 31 19461891
2021 Distinctive features of the Gac-Rsm pathway in plant-associated Pseudomonas. Environmental microbiology 30 33939255
2019 Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance. Molecular medicine reports 30 31257527
1998 HB-GAM/pleiotrophin: localization of mRNA and protein in the chicken developing leg. The International journal of developmental biology 29 9551864
2024 Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer. Cancer research 28 39024547
2021 A regulatory network involving Rpo, Gac and Rsm for nitrogen-fixing biofilm formation by Pseudomonas stutzeri. NPJ biofilms and microbiomes 28 34210981
2018 Phage Mu Gam protein promotes NHEJ in concert with Escherichia coli ligase. Proceedings of the National Academy of Sciences of the United States of America 28 30487222
2017 MiR-513c suppresses neuroblastoma cell migration, invasion, and proliferation through direct targeting glutaminase (GLS). Cancer biomarkers : section A of Disease markers 28 28800318
2017 Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells. Oncotarget 27 27902968
2022 SMYD2 Promotes Hepatocellular Carcinoma Progression by Reprogramming Glutamine Metabolism via c-Myc/GLS1 Axis. Cells 26 36611819
2019 Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors. Journal of medicinal chemistry 25 31603674
2023 Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, single-arm, phase II study. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 24 37875323
1986 Localization of the gam gene of bacteriophage mu and characterisation of the gene product. Gene 24 2952555
2023 Cytotoxicity Comparison between Drinking Water Treated by Chlorination with Postchloramination versus Granular Activated Carbon (GAC) with Postchlorination. Environmental science & technology 23 37640368
2021 Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Frontiers in oncology 22 34604074
2021 SIRT4 is the molecular switch mediating cellular proliferation in colorectal cancer through GLS mediated activation of AKT/GSK3β/CyclinD1 pathway. Carcinogenesis 21 33315089
2018 In Silico Preliminary Association of Ammonia Metabolism Genes GLS, CPS1, and GLUL with Risk of Alzheimer's Disease, Major Depressive Disorder, and Type 2 Diabetes. Journal of molecular neuroscience : MN 21 29441491
2004 Mechanical regulation of HB-GAM expression in bone cells. Biochemical and biophysical research communications 21 15184074
1999 Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes. Rheumatology (Oxford, England) 21 10587545
2022 Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis. Bioengineered 19 35313796
2020 Upregulation of GLS1 Isoforms KGA and GAC Facilitates Mitochondrial Metabolism and Cell Proliferation in Epstein-Barr Virus Infected Cells. Viruses 18 32727118
2017 Structure and Dynamics of DNA and RNA Double Helices of CAG and GAC Trinucleotide Repeats. Biophysical journal 18 28700917
2024 A novel mechanism of ferroptosis inhibition-enhanced atherosclerotic plaque stability: YAP1 suppresses vascular smooth muscle cell ferroptosis through GLS1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 39091212
2021 Circ_0000003 regulates glutamine metabolism and tumor progression of tongue squamous cell carcinoma via the miR‑330‑3p/GLS axis. Oncology reports 17 33649795
2020 Circ_0016418 promotes melanoma development and glutamine catabolism by regulating the miR-605-5p/GLS axis. International journal of clinical and experimental pathology 17 32782707
2024 GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells. Antioxidants (Basel, Switzerland) 16 38929183
2023 SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation. Matrix biology : journal of the International Society for Matrix Biology 16 37541633
2021 The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway. Infection and immunity 16 33168590
2020 NUDT21 suppresses the growth of small cell lung cancer by modulating GLS1 splicing. Biochemical and biophysical research communications 16 32228887
2018 GLS loss of function causes autosomal recessive spastic ataxia and optic atrophy. Annals of clinical and translational neurology 16 29468182
2025 CircPVT1 weakens miR-33a-5p unleashing the c-MYC/GLS1 metabolic axis in breast cancer. Journal of experimental & clinical cancer research : CR 15 40114244
2024 GLS1-mediated glutamine metabolism mitigates oxidative stress-induced matrix degradation, ferroptosis, and senescence in nucleus pulposus cells by modulating Fe2+ homeostasis. Free radical biology & medicine 15 39710108
1990 Purification of overexpressed gam gene protein from bacteriophage Mu by denaturation-renaturation techniques and a study of its DNA-binding properties. The Biochemical journal 15 2167662
2024 Brain acetylcholinesterase activity and the protective effect of Gac fruit on scopolamine-induced memory impairment in adult zebrafish. IBRO neuroscience reports 14 38435743
2023 Targeting glutaminase 1 (GLS1) by small molecules for anticancer therapeutics. European journal of medicinal chemistry 14 36996714
2022 Ozone and Fenton oxidation affected the bacterial community and opportunistic pathogens in biofilms and effluents from GAC. Water research 14 35489154
2022 HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells. Bioactive materials 14 36185739
2017 CmpX Affects Virulence in Pseudomonas aeruginosa Through the Gac/Rsm Signaling Pathway and by Modulating c-di-GMP Levels. The Journal of membrane biology 14 29063141
2007 Functional homology of gHs and gLs from EBV-related gamma-herpesviruses for EBV-induced membrane fusion. Virology 14 17477951
1996 Developmentally regulated neurite outgrowth response from dorsal root ganglion neurons to heparin-binding growth-associated molecule (HB-GAM) and the expression of HB-GAM in the targets of the developing dorsal root ganglion neurites. The European journal of neuroscience 14 8921256
2024 Gegen Qinlian Decoction reverses oxaliplatin resistance in colorectal cancer by inhibiting YTHDF1-regulated m6A modification of GLS1. Phytomedicine : international journal of phytotherapy and phytopharmacology 13 39089089
2023 GLS as a diagnostic biomarker in breast cancer: in-silico, in-situ, and in-vitro insights. Frontiers in oncology 13 37664031
2021 Dose escalation and expansion (phase Ia/Ib) study of GLS-010, a recombinant fully human antiprogrammed death-1 monoclonal antibody for advanced solid tumors or lymphoma. European journal of cancer (Oxford, England : 1990) 13 33691262
2021 Insight into the performance discrepancy of GAC and CAC as air-cathode materials in constructed wetland-microbial fuel cell system. The Science of the total environment 13 34863746
2018 Significance of neoadjuvant chemotherapy (NACT) in limb salvage treatment of osteosarcoma and its effect on GLS1 expression. European review for medical and pharmacological sciences 13 30338824
2001 The genetic dependence of RecBCD-Gam mediated double strand end repair in Escherichia coli. FEMS microbiology letters 13 11750819
2019 Inference of chromosome 3D structures from GAM data by a physics computational approach. Methods (San Diego, Calif.) 12 31604121
2023 LncRNA PVT1 Confers Cisplatin Resistance of Esophageal Cancer Cells through Modulating the miR-181a-5p-Glutaminase (GLS) Axis. Nutrition and cancer 11 37401860
2022 Direct Inhibition of RetS Synthesis by RsmA Contributes to Homeostasis of the Pseudomonas aeruginosa Gac/Rsm Signaling System. Journal of bacteriology 11 35041497
2022 Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac). Scientific reports 11 35110645
2021 Increased C reactive protein, cardiac troponin I and GLS are associated with myocardial inflammation in patients with non-ischemic heart failure. Scientific reports 11 33542341

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