{"gene":"GTPBP4","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2003,"finding":"NOG1 (GTPBP4) is required for biogenesis of the 60S ribosomal subunit; it co-sediments with 60S ribosomal subunits (not monosomes), co-precipitates 60S precursor RNAs, and localizes to the nucleolus, indicating association with a pre-60S precursor particle. RNAi knockdown dramatically decreases free 60S particles and causes failure to cleave ITS2 from pre-rRNA. Overexpression of a GTP-binding-defective mutant causes a 60S biogenesis defect and reduced processing of large subunit rRNAs.","method":"Sucrose density gradient sedimentation, RNA co-immunoprecipitation, RNA interference knockdown, dominant-negative overexpression in Trypanosoma brucei","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (co-sedimentation, co-IP, RNAi, dominant-negative), replicated across organisms","pmids":["12788953"],"is_preprint":false},{"year":2006,"finding":"In budding yeast, Nog1 forms a complex with 60S ribosomal proteins and pre-ribosomal proteins Nop7 and Rlp24. The Nog1 complex shuttles between the nucleolus and nucleoplasm for ribosome biogenesis. TOR kinase activity regulates late stages of ribosome maturation by controlling nucleolus-to-nucleoplasm translocation of this complex; nutrient depletion or TOR inactivation tethers the Nog1 complex to the nucleolus, arresting late-stage ribosome biogenesis. Subsequent loss of Nog1 and Nop7 leads to complete cessation of ribosome maturation.","method":"Co-immunoprecipitation, sucrose gradient sedimentation, rapamycin/nutrient-depletion epistasis, fluorescence localization in Saccharomyces cerevisiae","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, genetic epistasis with TOR, direct localization with functional consequence, multiple orthogonal methods","pmids":["16888624"],"is_preprint":false},{"year":2007,"finding":"In mouse cells, a point mutation restricting conformational flexibility of the switch II region of Nog1 (GTPBP4) creates a dominant-inhibitory phenotype: the mutant does not significantly affect GTP binding but disrupts productive pre-60S assembly, arrests cell proliferation, impairs processing of multiple pre-rRNA intermediates, causes degradation of nascent 5.8S/28S rRNA precursors, and leads to accumulation of enlarged pre-60S particles in the nucleolus, indicating that switch II conformational changes are critical for dissociation of preribosome-bound factors during intranucleolar maturation.","method":"Dominant-negative point mutagenesis (switch II region), sedimentation analysis of nucleolar preribosomes, pre-rRNA processing analysis in mouse cells","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — active-site mutagenesis with rigorous mechanistic follow-up (rRNA processing, sedimentation), single lab but multiple orthogonal readouts","pmids":["17785438"],"is_preprint":false},{"year":2007,"finding":"In S. cerevisiae, mutations in conserved GTP-binding pocket residues of Nog1 cause defects in cell growth and 60S ribosome assembly, but mutant proteins retain association with pre-60S particles. Association of Nog1 with pre-60S is independent of guanine nucleotide added to cell extracts. The N-terminal 126 amino acids are required for function; optimal pre-60S association requires sequences between amino acids 347–456. GTP-binding pocket mutations reduce levels of Nog1, Nop2, Nop15, and Tif6 in pre-60S particles.","method":"Site-directed mutagenesis of GTP-binding motifs, deletion analysis, isobaric labeling mass spectrometry of pre-60S particle composition, sucrose gradient sedimentation in S. cerevisiae","journal":"Molecular genetics and genomics","confidence":"High","confidence_rationale":"Tier 1 / Moderate — mutagenesis combined with MS-based particle composition analysis and sedimentation, single lab with multiple orthogonal methods","pmids":["17443350"],"is_preprint":false},{"year":2020,"finding":"The GTPase Nog1 coordinates assembly, maturation, and quality control of distant ribosomal functional centers on the pre-60S. Drg1-ATPase activity removes Rlp24 from Nog1 on the pre-60S; this extracts the C-terminal tail of Nog1 from the polypeptide exit tunnel (PET), enabling Rei1 to probe PET integrity and catalyze Arx1 release. Concomitantly, Nog1 eviction permits peptidyl transferase center maturation and allows Yvh1 to mediate Mrt4 release for stalk assembly. Thus Nog1 acts as a molecular placeholder coordinating sequential ATPase and GTPase activities during cytoplasmic pre-60S maturation.","method":"Cryo-EM structural analysis, genetic epistasis, biochemical reconstitution, mass spectrometry of pre-60S particle composition in S. cerevisiae","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure combined with genetic epistasis and biochemical reconstitution, multiple orthogonal methods","pmids":["31909713"],"is_preprint":false},{"year":2014,"finding":"In C. elegans, the nog-1 ortholog of GTPBP4 regulates growth, development, lifespan, and fat metabolism. GFP-tagged NOG-1 localizes to the nucleus, while aberrant NOG-1 concentrates in the nucleolus. Knockdown of nog-1 results in smaller brood size, slower growth, increased lifespan, and increased fat storage; overexpression decreases lifespan. Genetic evidence places nog-1 regulation of lifespan and fat storage via the insulin/IGF signaling pathway.","method":"RNAi knockdown, overexpression, GFP-fusion localization, lifespan and fat storage assays, genetic epistasis with insulin/IGF pathway in C. elegans","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic epistasis and direct localization experiment with functional consequences, single lab","pmids":["24552710"],"is_preprint":false},{"year":2018,"finding":"GTPBP4 interacts with p53 in gastric cancer cells, as detected by co-immunoprecipitation. Stable knockdown of GTPBP4 activates p53 and p53-related signaling pathways, inhibits cell proliferation, and promotes apoptosis, placing GTPBP4 upstream of p53 in this cancer context.","method":"Co-immunoprecipitation, RNA-based high-throughput sequencing, lentiviral stable knockdown, proliferation and apoptosis assays in gastric cancer cells","journal":"Cellular physiology and biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP with transcriptomic follow-up, single lab, no in vitro reconstitution","pmids":["29408813"],"is_preprint":false},{"year":2022,"finding":"GTPBP4 promotes aerobic glycolysis in hepatocellular carcinoma by inducing dimeric PKM2 formation through protein sumoylation. Mechanistically, GTPBP4 facilitates SUMO1 activation by UBA2 and acts as a linker bridging activated SUMO1 and PKM2 to induce PKM2 sumoylation. SUMO-modified PKM2 then translocates from the cytoplasm to the nucleus, contributing to HCC progression via EMT and STAT3 signaling. Promoter methylation by DNMT3A regulates GTPBP4 expression.","method":"Gain- and loss-of-function studies (in vitro and in vivo), co-immunoprecipitation, protein sumoylation assays, subcellular fractionation, mouse xenograft models","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, in vivo and in vitro gain/loss-of-function, sumoylation assay, single lab with multiple orthogonal methods","pmids":["36116159"],"is_preprint":false},{"year":2016,"finding":"GTPBP4 promotes colorectal carcinoma metastasis by disrupting the actin cytoskeleton through repression of RhoA signaling activity, as demonstrated by knockdown (which impedes cell motility) and ectopic overexpression (which enhances cell motility and metastasis).","method":"Knockdown and ectopic overexpression in colorectal cancer cells, cell motility/invasion assays, RhoA activity measurement","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single set of KD/OE experiments with limited mechanistic depth on RhoA pathway placement","pmids":["27720713"],"is_preprint":false},{"year":2023,"finding":"NOG1 (GTPBP4) negatively regulates type I interferon production by interacting with phosphorylated IRF3 and impairing its DNA-binding activity, thereby downregulating IFN-β transcription and downstream ISG expression. NOG1 overexpression inhibits viral RNA- and DNA-mediated IFN signaling; NOG1 deficiency promotes antiviral innate immune responses and resistance to VSV and HSV-1. The GTP-binding domain of NOG1 is required for this function.","method":"Overexpression and knockout (NOG1-deficient mice), co-immunoprecipitation with phospho-IRF3, DNA-binding activity assay, in vivo viral challenge (VSV, HSV-1), IFN-β ELISA","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with phospho-IRF3, functional domain mutagenesis (GTP-binding domain), in vivo mouse data and in vitro mechanistic assays, single lab","pmids":["37410776"],"is_preprint":false},{"year":2025,"finding":"GTPBP4 plays a role in ribosome biogenesis in coronary artery endothelial cells and was identified as a key target gene regulating ribosome biogenesis during myocardial fibrosis progression. Downregulation of GTPBP4 by apigenin suppressed EndMT and alleviated myocardial fibrosis in vitro and in vivo.","method":"Differential gene screening, knockdown in human coronary artery endothelial cells, in vitro EndMT model (TGF-β1-induced), in vivo animal fibrosis model","journal":"Human cell","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, KD with phenotypic readout but limited mechanistic depth on ribosome biogenesis pathway","pmids":["40938540"],"is_preprint":false}],"current_model":"GTPBP4 (NOG1) is a conserved nucleolar/nuclear GTPase of the Obg family that functions as a critical scaffold on pre-60S ribosomal particles: its C-terminal tail occupies the polypeptide exit tunnel as a placeholder, conformational changes in its switch II GTP-binding domain drive sequential release of assembly factors (Rlp24, Arx1, Mrt4) coordinated by upstream Drg1-ATPase activity, enabling peptidyl transferase center maturation, PET quality control, and stalk assembly; this process is regulated by TOR kinase, which controls nucleolus-to-nucleoplasm translocation of the Nog1–Nop7–Rlp24 complex in response to nutrients. Beyond ribosome biogenesis, mammalian GTPBP4 has additional roles: it interacts with and suppresses p53 in cancer cells, acts as a linker that induces PKM2 sumoylation to promote aerobic glycolysis, and negatively regulates innate antiviral immunity by binding phospho-IRF3 via its GTP-binding domain to impair IRF3 DNA-binding and IFN-β transcription."},"narrative":{"mechanistic_narrative":"GTPBP4 (NOG1) is a conserved nucleolar Obg-family GTPase that functions as a critical scaffold during 60S ribosomal subunit biogenesis [PMID:12788953, PMID:31909713]. It associates with pre-60S precursor particles, co-sedimenting with 60S subunits and binding 60S precursor RNAs, and its loss blocks ITS2 cleavage and processing of large-subunit rRNAs, depleting free 60S particles [PMID:12788953]. Within the assembling particle GTPBP4 acts as a molecular placeholder: its C-terminal tail occupies the polypeptide exit tunnel, and Drg1-ATPase-driven removal of Rlp24 extracts this tail, coordinating Rei1-mediated exit-tunnel quality control, Arx1 release, peptidyl transferase center maturation, and Yvh1-dependent Mrt4 release for stalk assembly [PMID:31909713]. Conformational changes in the switch II region of its GTP-binding domain drive these maturation steps; a switch II mutant that retains GTP binding still arrests pre-60S assembly, causing accumulation of enlarged nucleolar pre-60S particles and degradation of nascent rRNA precursors [PMID:17785438, PMID:17443350]. The Nog1–Nop7–Rlp24 complex shuttles between nucleolus and nucleoplasm, and TOR kinase governs this translocation in response to nutrients, coupling late ribosome maturation to nutrient status [PMID:16888624]. In mammalian cancer cells GTPBP4 acquires additional regulatory roles: it binds and suppresses p53, with knockdown activating p53 signaling and apoptosis [PMID:29408813], and it bridges activated SUMO1 to PKM2 to induce PKM2 sumoylation and promote aerobic glycolysis [PMID:36116159]. GTPBP4 also negatively regulates innate antiviral immunity by binding phosphorylated IRF3 through its GTP-binding domain, impairing IRF3 DNA binding and IFN-β transcription [PMID:37410776].","teleology":[{"year":2003,"claim":"Established that GTPBP4/NOG1 is a nucleolar factor essential for 60S subunit biogenesis rather than a general translation factor, by localizing its function to a specific pre-60S maturation step.","evidence":"Co-sedimentation, RNA co-IP, RNAi knockdown and dominant-negative GTP-binding mutant in Trypanosoma brucei","pmids":["12788953"],"confidence":"High","gaps":["Did not resolve where on the pre-60S particle Nog1 binds","Catalytic role of the GTPase domain not mechanistically defined"]},{"year":2006,"claim":"Showed that the Nog1 complex with Nop7 and Rlp24 physically shuttles between nucleolus and nucleoplasm and that this trafficking is the regulatory node controlled by TOR/nutrient signaling for late ribosome maturation.","evidence":"Reciprocal Co-IP, sucrose gradient sedimentation, rapamycin/nutrient-depletion epistasis and localization in S. cerevisiae","pmids":["16888624"],"confidence":"High","gaps":["Molecular mechanism by which TOR controls Nog1 translocation not defined","Does not specify which maturation reactions occur in nucleolus vs nucleoplasm"]},{"year":2007,"claim":"Defined the switch II conformational cycle as the functional core: a switch II mutant that retains GTP binding still blocks pre-60S assembly, separating nucleotide binding from productive factor dissociation.","evidence":"Switch II point mutagenesis, nucleolar preribosome sedimentation and pre-rRNA processing analysis in mouse cells","pmids":["17785438"],"confidence":"High","gaps":["Direct factors released by switch II movement not identified at this stage","GTP hydrolysis activity not quantified"]},{"year":2007,"claim":"Mapped the domain requirements of Nog1, showing pre-60S association is nucleotide-independent and that GTP-pocket integrity controls recruitment of downstream assembly factors.","evidence":"Site-directed mutagenesis of GTP-binding motifs, deletion analysis, isobaric-labeling MS of pre-60S composition and sedimentation in S. cerevisiae","pmids":["17443350"],"confidence":"High","gaps":["Whether nucleotide state changes during the assembly cycle in vivo unresolved","Order of factor recruitment/release not established"]},{"year":2020,"claim":"Resolved Nog1 as a molecular placeholder whose C-terminal tail in the polypeptide exit tunnel coordinates sequential Drg1-ATPase and GTPase activities to orchestrate quality control and maturation of distant functional centers on the pre-60S.","evidence":"Cryo-EM, genetic epistasis, biochemical reconstitution and MS of pre-60S composition in S. cerevisiae","pmids":["31909713"],"confidence":"High","gaps":["Timing and trigger of GTP hydrolysis during eviction not fully defined","Conservation of the precise placeholder mechanism in mammals not directly tested"]},{"year":2014,"claim":"Connected ribosome-biogenesis dosage of NOG1 to organismal physiology, linking it to growth, lifespan and fat metabolism through insulin/IGF signaling.","evidence":"RNAi, overexpression, GFP-fusion localization and lifespan/fat assays with insulin/IGF epistasis in C. elegans","pmids":["24552710"],"confidence":"Medium","gaps":["Whether physiological effects are solely downstream of ribosome biogenesis unclear","Direct molecular link to insulin/IGF components not established"]},{"year":2016,"claim":"Proposed an extraribosomal role in cell motility, linking GTPBP4 to colorectal metastasis through repression of RhoA-dependent actin remodeling.","evidence":"Knockdown and overexpression with motility/invasion assays and RhoA activity measurement in colorectal cancer cells","pmids":["27720713"],"confidence":"Low","gaps":["Single lab with limited mechanistic placement of GTPBP4 relative to RhoA","No direct physical interaction demonstrated"]},{"year":2018,"claim":"Identified GTPBP4 as a negative regulator of p53, providing a mechanistic basis for its pro-proliferative role in cancer.","evidence":"Co-IP, RNA-seq, stable knockdown and proliferation/apoptosis assays in gastric cancer cells","pmids":["29408813"],"confidence":"Medium","gaps":["No in vitro reconstitution of the GTPBP4-p53 interaction","Domain mediating p53 binding not mapped"]},{"year":2022,"claim":"Established a non-ribosomal enzymatic-adaptor function: GTPBP4 bridges activated SUMO1 to PKM2, driving PKM2 sumoylation and aerobic glycolysis in hepatocellular carcinoma.","evidence":"Co-IP, sumoylation assays, subcellular fractionation, gain/loss-of-function and xenografts","pmids":["36116159"],"confidence":"Medium","gaps":["Whether this linker activity requires the GTPase domain not tested","Generality beyond HCC unknown"]},{"year":2023,"claim":"Defined a role in innate immunity: GTPBP4 uses its GTP-binding domain to bind phospho-IRF3 and block its DNA binding, dampening type I interferon responses.","evidence":"Overexpression, knockout mice, Co-IP with phospho-IRF3, DNA-binding assay and in vivo VSV/HSV-1 challenge","pmids":["37410776"],"confidence":"Medium","gaps":["Whether GTP hydrolysis is required for IRF3 inhibition not resolved","Relationship between nucleolar pool and cytoplasmic IRF3 regulation unclear"]},{"year":2025,"claim":"Implicated GTPBP4-dependent ribosome biogenesis in endothelial-to-mesenchymal transition and myocardial fibrosis as a druggable target.","evidence":"Differential gene screening, knockdown in coronary artery endothelial cells, TGF-β1 EndMT model and in vivo fibrosis model","pmids":["40938540"],"confidence":"Low","gaps":["Limited mechanistic depth linking GTPBP4 to ribosome biogenesis in this context","Direct apigenin-GTPBP4 relationship not biochemically established"]},{"year":null,"claim":"How GTPBP4's conserved ribosome-assembly GTPase activity mechanistically relates to its mammalian extraribosomal functions (p53 suppression, PKM2 sumoylation, IRF3 inhibition) remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of mammalian GTPBP4 bound to p53, PKM2 or IRF3","Whether the GTP-binding domain and switch II cycle are used in non-ribosomal interactions untested","Whether moonlighting functions reflect cytoplasmic relocalization of a normally nucleolar protein unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0,2,3,4]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[4,7]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0,2,5]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,4]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[9]}],"complexes":["Nog1–Nop7–Rlp24 pre-60S complex"],"partners":["NOP7","RLP24","TP53","PKM2","SUMO1","UBA2","IRF3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BZE4","full_name":"GTP-binding protein 4","aliases":["Chronic renal failure gene protein","GTP-binding protein NGB","Nucleolar GTP-binding protein 1"],"length_aa":634,"mass_kda":74.0,"function":"Involved in the biogenesis of the 60S ribosomal subunit (PubMed:32669547). Acts as a TP53 repressor, preventing TP53 stabilization and cell cycle arrest (PubMed:20308539)","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9BZE4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/GTPBP4","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000107937","cell_line_id":"CID001065","localizations":[{"compartment":"nucleolus_gc","grade":3}],"interactors":[{"gene":"CTCF","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"G3BP2","stoichiometry":0.2},{"gene":"ILF3","stoichiometry":0.2},{"gene":"LMNB1","stoichiometry":0.2},{"gene":"MAPRE1","stoichiometry":0.2},{"gene":"METAP2","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"PSPC1","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001065","total_profiled":1310},"omim":[{"mim_id":"619169","title":"GTP-BINDING PROTEIN 4; GTPBP4","url":"https://www.omim.org/entry/619169"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"},{"location":"Nucleoli rim","reliability":"Supported"},{"location":"Nuclear membrane","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GTPBP4"},"hgnc":{"alias_symbol":["CRFG","NGB","FLJ10690","FLJ10686","NOG1"],"prev_symbol":[]},"alphafold":{"accession":"Q9BZE4","domains":[{"cath_id":"1.20.120.1190","chopping":"5-159","consensus_level":"high","plddt":93.4295,"start":5,"end":159},{"cath_id":"3.40.50.300","chopping":"169-349","consensus_level":"high","plddt":86.9073,"start":169,"end":349}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BZE4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BZE4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BZE4-F1-predicted_aligned_error_v6.png","plddt_mean":83.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GTPBP4","jax_strain_url":"https://www.jax.org/strain/search?query=GTPBP4"},"sequence":{"accession":"Q9BZE4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BZE4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BZE4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BZE4"}},"corpus_meta":[{"pmid":"12788953","id":"PMC_12788953","title":"The NOG1 GTP-binding protein is required for biogenesis of the 60 S ribosomal subunit.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12788953","citation_count":79,"is_preprint":false},{"pmid":"36116159","id":"PMC_36116159","title":"GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism.","date":"2022","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/36116159","citation_count":67,"is_preprint":false},{"pmid":"16888624","id":"PMC_16888624","title":"TOR regulates late steps of ribosome maturation in the nucleoplasm via Nog1 in response to nutrients.","date":"2006","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/16888624","citation_count":45,"is_preprint":false},{"pmid":"31909713","id":"PMC_31909713","title":"The GTPase Nog1 co-ordinates the assembly, maturation and quality control of distant ribosomal functional centers.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/31909713","citation_count":35,"is_preprint":false},{"pmid":"28835689","id":"PMC_28835689","title":"The small GTPase, nucleolar GTP-binding protein 1 (NOG1), has a novel role in plant innate immunity.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28835689","citation_count":29,"is_preprint":false},{"pmid":"17443350","id":"PMC_17443350","title":"In vivo functional characterization of the Saccharomyces cerevisiae 60S biogenesis GTPase Nog1.","date":"2007","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/17443350","citation_count":28,"is_preprint":false},{"pmid":"27720713","id":"PMC_27720713","title":"Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis.","date":"2016","source":"Biochemical and biophysical research 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genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36437935","citation_count":2,"is_preprint":false},{"pmid":"40938540","id":"PMC_40938540","title":"Apigenin inhibits endothelial-to-mesenchymal transition of coronary artery endothelial cells and myocardial fibrosis by regulating ribosome biogenesis through GTPBP4 modulation.","date":"2025","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/40938540","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11313,"output_tokens":3472,"usd":0.043009,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11038,"output_tokens":3995,"usd":0.077533,"stage2_stop_reason":"end_turn"},"total_usd":0.120542,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"NOG1 (GTPBP4) is required for biogenesis of the 60S ribosomal subunit; it co-sediments with 60S ribosomal subunits (not monosomes), co-precipitates 60S precursor RNAs, and localizes to the nucleolus, indicating association with a pre-60S precursor particle. RNAi knockdown dramatically decreases free 60S particles and causes failure to cleave ITS2 from pre-rRNA. Overexpression of a GTP-binding-defective mutant causes a 60S biogenesis defect and reduced processing of large subunit rRNAs.\",\n      \"method\": \"Sucrose density gradient sedimentation, RNA co-immunoprecipitation, RNA interference knockdown, dominant-negative overexpression in Trypanosoma brucei\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (co-sedimentation, co-IP, RNAi, dominant-negative), replicated across organisms\",\n      \"pmids\": [\"12788953\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"In budding yeast, Nog1 forms a complex with 60S ribosomal proteins and pre-ribosomal proteins Nop7 and Rlp24. The Nog1 complex shuttles between the nucleolus and nucleoplasm for ribosome biogenesis. TOR kinase activity regulates late stages of ribosome maturation by controlling nucleolus-to-nucleoplasm translocation of this complex; nutrient depletion or TOR inactivation tethers the Nog1 complex to the nucleolus, arresting late-stage ribosome biogenesis. Subsequent loss of Nog1 and Nop7 leads to complete cessation of ribosome maturation.\",\n      \"method\": \"Co-immunoprecipitation, sucrose gradient sedimentation, rapamycin/nutrient-depletion epistasis, fluorescence localization in Saccharomyces cerevisiae\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, genetic epistasis with TOR, direct localization with functional consequence, multiple orthogonal methods\",\n      \"pmids\": [\"16888624\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In mouse cells, a point mutation restricting conformational flexibility of the switch II region of Nog1 (GTPBP4) creates a dominant-inhibitory phenotype: the mutant does not significantly affect GTP binding but disrupts productive pre-60S assembly, arrests cell proliferation, impairs processing of multiple pre-rRNA intermediates, causes degradation of nascent 5.8S/28S rRNA precursors, and leads to accumulation of enlarged pre-60S particles in the nucleolus, indicating that switch II conformational changes are critical for dissociation of preribosome-bound factors during intranucleolar maturation.\",\n      \"method\": \"Dominant-negative point mutagenesis (switch II region), sedimentation analysis of nucleolar preribosomes, pre-rRNA processing analysis in mouse cells\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site mutagenesis with rigorous mechanistic follow-up (rRNA processing, sedimentation), single lab but multiple orthogonal readouts\",\n      \"pmids\": [\"17785438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"In S. cerevisiae, mutations in conserved GTP-binding pocket residues of Nog1 cause defects in cell growth and 60S ribosome assembly, but mutant proteins retain association with pre-60S particles. Association of Nog1 with pre-60S is independent of guanine nucleotide added to cell extracts. The N-terminal 126 amino acids are required for function; optimal pre-60S association requires sequences between amino acids 347–456. GTP-binding pocket mutations reduce levels of Nog1, Nop2, Nop15, and Tif6 in pre-60S particles.\",\n      \"method\": \"Site-directed mutagenesis of GTP-binding motifs, deletion analysis, isobaric labeling mass spectrometry of pre-60S particle composition, sucrose gradient sedimentation in S. cerevisiae\",\n      \"journal\": \"Molecular genetics and genomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — mutagenesis combined with MS-based particle composition analysis and sedimentation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"17443350\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The GTPase Nog1 coordinates assembly, maturation, and quality control of distant ribosomal functional centers on the pre-60S. Drg1-ATPase activity removes Rlp24 from Nog1 on the pre-60S; this extracts the C-terminal tail of Nog1 from the polypeptide exit tunnel (PET), enabling Rei1 to probe PET integrity and catalyze Arx1 release. Concomitantly, Nog1 eviction permits peptidyl transferase center maturation and allows Yvh1 to mediate Mrt4 release for stalk assembly. Thus Nog1 acts as a molecular placeholder coordinating sequential ATPase and GTPase activities during cytoplasmic pre-60S maturation.\",\n      \"method\": \"Cryo-EM structural analysis, genetic epistasis, biochemical reconstitution, mass spectrometry of pre-60S particle composition in S. cerevisiae\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure combined with genetic epistasis and biochemical reconstitution, multiple orthogonal methods\",\n      \"pmids\": [\"31909713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In C. elegans, the nog-1 ortholog of GTPBP4 regulates growth, development, lifespan, and fat metabolism. GFP-tagged NOG-1 localizes to the nucleus, while aberrant NOG-1 concentrates in the nucleolus. Knockdown of nog-1 results in smaller brood size, slower growth, increased lifespan, and increased fat storage; overexpression decreases lifespan. Genetic evidence places nog-1 regulation of lifespan and fat storage via the insulin/IGF signaling pathway.\",\n      \"method\": \"RNAi knockdown, overexpression, GFP-fusion localization, lifespan and fat storage assays, genetic epistasis with insulin/IGF pathway in C. elegans\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic epistasis and direct localization experiment with functional consequences, single lab\",\n      \"pmids\": [\"24552710\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"GTPBP4 interacts with p53 in gastric cancer cells, as detected by co-immunoprecipitation. Stable knockdown of GTPBP4 activates p53 and p53-related signaling pathways, inhibits cell proliferation, and promotes apoptosis, placing GTPBP4 upstream of p53 in this cancer context.\",\n      \"method\": \"Co-immunoprecipitation, RNA-based high-throughput sequencing, lentiviral stable knockdown, proliferation and apoptosis assays in gastric cancer cells\",\n      \"journal\": \"Cellular physiology and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP with transcriptomic follow-up, single lab, no in vitro reconstitution\",\n      \"pmids\": [\"29408813\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"GTPBP4 promotes aerobic glycolysis in hepatocellular carcinoma by inducing dimeric PKM2 formation through protein sumoylation. Mechanistically, GTPBP4 facilitates SUMO1 activation by UBA2 and acts as a linker bridging activated SUMO1 and PKM2 to induce PKM2 sumoylation. SUMO-modified PKM2 then translocates from the cytoplasm to the nucleus, contributing to HCC progression via EMT and STAT3 signaling. Promoter methylation by DNMT3A regulates GTPBP4 expression.\",\n      \"method\": \"Gain- and loss-of-function studies (in vitro and in vivo), co-immunoprecipitation, protein sumoylation assays, subcellular fractionation, mouse xenograft models\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, in vivo and in vitro gain/loss-of-function, sumoylation assay, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"36116159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GTPBP4 promotes colorectal carcinoma metastasis by disrupting the actin cytoskeleton through repression of RhoA signaling activity, as demonstrated by knockdown (which impedes cell motility) and ectopic overexpression (which enhances cell motility and metastasis).\",\n      \"method\": \"Knockdown and ectopic overexpression in colorectal cancer cells, cell motility/invasion assays, RhoA activity measurement\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single set of KD/OE experiments with limited mechanistic depth on RhoA pathway placement\",\n      \"pmids\": [\"27720713\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NOG1 (GTPBP4) negatively regulates type I interferon production by interacting with phosphorylated IRF3 and impairing its DNA-binding activity, thereby downregulating IFN-β transcription and downstream ISG expression. NOG1 overexpression inhibits viral RNA- and DNA-mediated IFN signaling; NOG1 deficiency promotes antiviral innate immune responses and resistance to VSV and HSV-1. The GTP-binding domain of NOG1 is required for this function.\",\n      \"method\": \"Overexpression and knockout (NOG1-deficient mice), co-immunoprecipitation with phospho-IRF3, DNA-binding activity assay, in vivo viral challenge (VSV, HSV-1), IFN-β ELISA\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with phospho-IRF3, functional domain mutagenesis (GTP-binding domain), in vivo mouse data and in vitro mechanistic assays, single lab\",\n      \"pmids\": [\"37410776\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GTPBP4 plays a role in ribosome biogenesis in coronary artery endothelial cells and was identified as a key target gene regulating ribosome biogenesis during myocardial fibrosis progression. Downregulation of GTPBP4 by apigenin suppressed EndMT and alleviated myocardial fibrosis in vitro and in vivo.\",\n      \"method\": \"Differential gene screening, knockdown in human coronary artery endothelial cells, in vitro EndMT model (TGF-β1-induced), in vivo animal fibrosis model\",\n      \"journal\": \"Human cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, KD with phenotypic readout but limited mechanistic depth on ribosome biogenesis pathway\",\n      \"pmids\": [\"40938540\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GTPBP4 (NOG1) is a conserved nucleolar/nuclear GTPase of the Obg family that functions as a critical scaffold on pre-60S ribosomal particles: its C-terminal tail occupies the polypeptide exit tunnel as a placeholder, conformational changes in its switch II GTP-binding domain drive sequential release of assembly factors (Rlp24, Arx1, Mrt4) coordinated by upstream Drg1-ATPase activity, enabling peptidyl transferase center maturation, PET quality control, and stalk assembly; this process is regulated by TOR kinase, which controls nucleolus-to-nucleoplasm translocation of the Nog1–Nop7–Rlp24 complex in response to nutrients. Beyond ribosome biogenesis, mammalian GTPBP4 has additional roles: it interacts with and suppresses p53 in cancer cells, acts as a linker that induces PKM2 sumoylation to promote aerobic glycolysis, and negatively regulates innate antiviral immunity by binding phospho-IRF3 via its GTP-binding domain to impair IRF3 DNA-binding and IFN-β transcription.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GTPBP4 (NOG1) is a conserved nucleolar Obg-family GTPase that functions as a critical scaffold during 60S ribosomal subunit biogenesis [#0, #4]. It associates with pre-60S precursor particles, co-sedimenting with 60S subunits and binding 60S precursor RNAs, and its loss blocks ITS2 cleavage and processing of large-subunit rRNAs, depleting free 60S particles [#0]. Within the assembling particle GTPBP4 acts as a molecular placeholder: its C-terminal tail occupies the polypeptide exit tunnel, and Drg1-ATPase-driven removal of Rlp24 extracts this tail, coordinating Rei1-mediated exit-tunnel quality control, Arx1 release, peptidyl transferase center maturation, and Yvh1-dependent Mrt4 release for stalk assembly [#4]. Conformational changes in the switch II region of its GTP-binding domain drive these maturation steps; a switch II mutant that retains GTP binding still arrests pre-60S assembly, causing accumulation of enlarged nucleolar pre-60S particles and degradation of nascent rRNA precursors [#2, #3]. The Nog1\\u2013Nop7\\u2013Rlp24 complex shuttles between nucleolus and nucleoplasm, and TOR kinase governs this translocation in response to nutrients, coupling late ribosome maturation to nutrient status [#1]. In mammalian cancer cells GTPBP4 acquires additional regulatory roles: it binds and suppresses p53, with knockdown activating p53 signaling and apoptosis [#6], and it bridges activated SUMO1 to PKM2 to induce PKM2 sumoylation and promote aerobic glycolysis [#7]. GTPBP4 also negatively regulates innate antiviral immunity by binding phosphorylated IRF3 through its GTP-binding domain, impairing IRF3 DNA binding and IFN-\\u03b2 transcription [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that GTPBP4/NOG1 is a nucleolar factor essential for 60S subunit biogenesis rather than a general translation factor, by localizing its function to a specific pre-60S maturation step.\",\n      \"evidence\": \"Co-sedimentation, RNA co-IP, RNAi knockdown and dominant-negative GTP-binding mutant in Trypanosoma brucei\",\n      \"pmids\": [\"12788953\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve where on the pre-60S particle Nog1 binds\", \"Catalytic role of the GTPase domain not mechanistically defined\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Showed that the Nog1 complex with Nop7 and Rlp24 physically shuttles between nucleolus and nucleoplasm and that this trafficking is the regulatory node controlled by TOR/nutrient signaling for late ribosome maturation.\",\n      \"evidence\": \"Reciprocal Co-IP, sucrose gradient sedimentation, rapamycin/nutrient-depletion epistasis and localization in S. cerevisiae\",\n      \"pmids\": [\"16888624\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which TOR controls Nog1 translocation not defined\", \"Does not specify which maturation reactions occur in nucleolus vs nucleoplasm\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined the switch II conformational cycle as the functional core: a switch II mutant that retains GTP binding still blocks pre-60S assembly, separating nucleotide binding from productive factor dissociation.\",\n      \"evidence\": \"Switch II point mutagenesis, nucleolar preribosome sedimentation and pre-rRNA processing analysis in mouse cells\",\n      \"pmids\": [\"17785438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct factors released by switch II movement not identified at this stage\", \"GTP hydrolysis activity not quantified\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Mapped the domain requirements of Nog1, showing pre-60S association is nucleotide-independent and that GTP-pocket integrity controls recruitment of downstream assembly factors.\",\n      \"evidence\": \"Site-directed mutagenesis of GTP-binding motifs, deletion analysis, isobaric-labeling MS of pre-60S composition and sedimentation in S. cerevisiae\",\n      \"pmids\": [\"17443350\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether nucleotide state changes during the assembly cycle in vivo unresolved\", \"Order of factor recruitment/release not established\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolved Nog1 as a molecular placeholder whose C-terminal tail in the polypeptide exit tunnel coordinates sequential Drg1-ATPase and GTPase activities to orchestrate quality control and maturation of distant functional centers on the pre-60S.\",\n      \"evidence\": \"Cryo-EM, genetic epistasis, biochemical reconstitution and MS of pre-60S composition in S. cerevisiae\",\n      \"pmids\": [\"31909713\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Timing and trigger of GTP hydrolysis during eviction not fully defined\", \"Conservation of the precise placeholder mechanism in mammals not directly tested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected ribosome-biogenesis dosage of NOG1 to organismal physiology, linking it to growth, lifespan and fat metabolism through insulin/IGF signaling.\",\n      \"evidence\": \"RNAi, overexpression, GFP-fusion localization and lifespan/fat assays with insulin/IGF epistasis in C. elegans\",\n      \"pmids\": [\"24552710\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether physiological effects are solely downstream of ribosome biogenesis unclear\", \"Direct molecular link to insulin/IGF components not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Proposed an extraribosomal role in cell motility, linking GTPBP4 to colorectal metastasis through repression of RhoA-dependent actin remodeling.\",\n      \"evidence\": \"Knockdown and overexpression with motility/invasion assays and RhoA activity measurement in colorectal cancer cells\",\n      \"pmids\": [\"27720713\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single lab with limited mechanistic placement of GTPBP4 relative to RhoA\", \"No direct physical interaction demonstrated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identified GTPBP4 as a negative regulator of p53, providing a mechanistic basis for its pro-proliferative role in cancer.\",\n      \"evidence\": \"Co-IP, RNA-seq, stable knockdown and proliferation/apoptosis assays in gastric cancer cells\",\n      \"pmids\": [\"29408813\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro reconstitution of the GTPBP4-p53 interaction\", \"Domain mediating p53 binding not mapped\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established a non-ribosomal enzymatic-adaptor function: GTPBP4 bridges activated SUMO1 to PKM2, driving PKM2 sumoylation and aerobic glycolysis in hepatocellular carcinoma.\",\n      \"evidence\": \"Co-IP, sumoylation assays, subcellular fractionation, gain/loss-of-function and xenografts\",\n      \"pmids\": [\"36116159\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this linker activity requires the GTPase domain not tested\", \"Generality beyond HCC unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a role in innate immunity: GTPBP4 uses its GTP-binding domain to bind phospho-IRF3 and block its DNA binding, dampening type I interferon responses.\",\n      \"evidence\": \"Overexpression, knockout mice, Co-IP with phospho-IRF3, DNA-binding assay and in vivo VSV/HSV-1 challenge\",\n      \"pmids\": [\"37410776\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether GTP hydrolysis is required for IRF3 inhibition not resolved\", \"Relationship between nucleolar pool and cytoplasmic IRF3 regulation unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated GTPBP4-dependent ribosome biogenesis in endothelial-to-mesenchymal transition and myocardial fibrosis as a druggable target.\",\n      \"evidence\": \"Differential gene screening, knockdown in coronary artery endothelial cells, TGF-\\u03b21 EndMT model and in vivo fibrosis model\",\n      \"pmids\": [\"40938540\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Limited mechanistic depth linking GTPBP4 to ribosome biogenesis in this context\", \"Direct apigenin-GTPBP4 relationship not biochemically established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GTPBP4's conserved ribosome-assembly GTPase activity mechanistically relates to its mammalian extraribosomal functions (p53 suppression, PKM2 sumoylation, IRF3 inhibition) remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of mammalian GTPBP4 bound to p53, PKM2 or IRF3\", \"Whether the GTP-binding domain and switch II cycle are used in non-ribosomal interactions untested\", \"Whether moonlighting functions reflect cytoplasmic relocalization of a normally nucleolar protein unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 2, 3, 4]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0, 2, 5]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"complexes\": [\n      \"Nog1\\u2013Nop7\\u2013Rlp24 pre-60S complex\"\n    ],\n    \"partners\": [\n      \"NOP7\",\n      \"RLP24\",\n      \"TP53\",\n      \"PKM2\",\n      \"SUMO1\",\n      \"UBA2\",\n      \"IRF3\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}