{"gene":"NUP37","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2012,"finding":"Crystal structure of S. pombe Nup37 in complex with Nup120 (a 174-kDa subassembly forming one short arm of the Y-complex) shows that Nup37 binds near the bend of the L-shaped Nup120 protein, potentially stabilizing the relative orientation of its two domains; reconstitution assays pinpointed residues crucial for this interaction; in vivo and in vitro results showed ELY5/ELYS binds near the Nup120-Nup37 interface; both Nup37 and ELY5 integrate directly via Nup120/160 into the heptameric Y-complex.","method":"X-ray crystallography, reconstitution assays, in vitro binding assays, cell biological experiments","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with reconstitution assays and mutagenesis in a single rigorous study, with both in vitro and in vivo validation","pmids":["22955883"],"is_preprint":false},{"year":2017,"finding":"NUP37 interacts with YAP protein and enhances the interaction between YAP and TEAD, thereby activating YAP/TEAD transcriptional signaling; knockdown of NUP37 inhibited HCC cell growth, migration, invasion, and metastasis.","method":"Co-immunoprecipitation, overexpression and knockdown experiments, cell growth/migration/invasion assays, in vivo mouse model","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP interaction and functional knockdown/overexpression with multiple phenotypic readouts, single lab","pmids":["29228669"],"is_preprint":false},{"year":2024,"finding":"TRIM28 was identified as an interacting protein of NUP37 and upregulates NUP37 protein levels; TRIM28-mediated SUMOylation of NUP37 at Lys114/118/246 inhibits K27-linked polyubiquitination of NUP37, thereby blocking its proteasomal degradation and increasing NUP37 protein stability, which promotes lipid synthesis and HCC progression.","method":"Co-immunoprecipitation, western blotting, mutagenesis (SUMOylation site identification), ubiquitination assays, xenograft mouse models","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus site-specific mutagenesis and ubiquitination assays in a single lab study","pmids":["39294431"],"is_preprint":false},{"year":2024,"finding":"NUP37 interacts with DNMT1 and promotes proliferation and invasion of glioma cells through this interaction; overexpression of DNMT1 rescued the adverse effects caused by NUP37 depletion, placing NUP37 upstream of DNMT1-mediated DNA methylation in glioma.","method":"Co-immunoprecipitation, knockdown/overexpression experiments, cell proliferation and invasion assays","journal":"Cell death discovery","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP interaction and epistasis rescue experiment reported in a single lab with limited mechanistic detail in abstract","pmids":["39174498"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B physically binds NUP37 (verified by co-immunoprecipitation) and acts upstream of NUP37; NUP37 overexpression reversed the inhibitory effects of DEPDC1B silencing on CRC cell proliferation, migration, invasion, and PI3K/AKT signaling, placing NUP37 downstream of DEPDC1B in this pathway.","method":"Co-immunoprecipitation, siRNA knockdown, overexpression rescue, flow cytometry, western blotting, in vivo xenograft","journal":"Molecular medicine reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP and epistasis rescue, single lab, limited mechanistic resolution in abstract","pmids":["37203403"],"is_preprint":false},{"year":2026,"finding":"ASCL1 directly binds the NUP37 promoter and suppresses NUP37 transcription; NUP37 knockdown enhanced ASCL1/miR124/p53shRNA-mediated transdifferentiation and nuclear shrinkage, while NUP37 overexpression had the opposite effect, establishing NUP37 as a regulator of nuclear pore complex abundance and nuclear size during neuronal conversion.","method":"Chromatin binding assay (ASCL1 promoter binding), knockdown and overexpression experiments, live-cell imaging of nuclear size during transdifferentiation","journal":"Stem cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct promoter binding plus bidirectional genetic manipulation (KD and OE) with quantitative nuclear size phenotype in a single study","pmids":["41759523"],"is_preprint":false}],"current_model":"NUP37 is a nucleoporin that integrates into the heptameric Y-complex by binding directly to Nup120/160 (structurally defined by crystal structure and reconstitution), regulates nuclear pore complex abundance and thereby nuclear size (suppressed transcriptionally by ASCL1), interacts with YAP to enhance YAP-TEAD signaling, is stabilized post-translationally by TRIM28-mediated SUMOylation at Lys114/118/246 that blocks K27-polyubiquitination and proteasomal degradation, and promotes tumor cell proliferation and invasion in multiple cancers through interactions with DNMT1 and downstream of DEPDC1B via PI3K/AKT signaling."},"narrative":{"mechanistic_narrative":"NUP37 is a structural nucleoporin that integrates directly into the heptameric Y-complex of the nuclear pore through binding to Nup120/160, where it docks near the bend of the L-shaped Nup120 subunit and stabilizes the relative orientation of its two domains adjacent to the ELYS-binding interface [PMID:22955883]. Beyond its architectural role, NUP37 governs nuclear pore complex abundance and thereby nuclear size, a function placed under transcriptional control by ASCL1, which directly binds the NUP37 promoter to repress its expression during neuronal transdifferentiation [PMID:41759523]. NUP37 protein levels are further set post-translationally: TRIM28 binds NUP37 and SUMOylates it at Lys114/118/246, blocking K27-linked polyubiquitination and proteasomal degradation to stabilize the protein [PMID:39294431]. In cancer contexts, NUP37 acts as a pro-tumorigenic effector, interacting with YAP to enhance YAP-TEAD transcriptional signaling and driving hepatocellular carcinoma growth, migration, and invasion [PMID:29228669].","teleology":[{"year":2012,"claim":"Established how NUP37 is built into the nuclear pore — defining it as a direct structural subunit of the Y-complex rather than a peripheral associate.","evidence":"X-ray crystallography of S. pombe Nup37-Nup120 subassembly with reconstitution and mutagenesis","pmids":["22955883"],"confidence":"High","gaps":["Structure is from S. pombe; human Y-complex architecture not directly resolved here","Functional consequence of the Nup37-Nup120 interface for pore assembly in vivo not quantified","Does not address regulation of NUP37 abundance or its non-structural roles"]},{"year":2017,"claim":"Connected NUP37 to oncogenic transcription by showing it physically enhances YAP-TEAD signaling, moving it beyond a purely architectural role.","evidence":"Co-IP, knockdown/overexpression, growth/migration/invasion assays and mouse model in HCC","pmids":["29228669"],"confidence":"Medium","gaps":["Direct vs indirect nature of the NUP37-YAP interaction not structurally resolved","Whether this depends on NUP37's nuclear pore role is unclear","Single-lab finding without reciprocal validation"]},{"year":2023,"claim":"Placed NUP37 as a downstream effector of DEPDC1B/PI3K-AKT signaling in colorectal cancer via physical binding and epistasis rescue.","evidence":"Co-IP, siRNA knockdown, overexpression rescue, xenograft in CRC","pmids":["37203403"],"confidence":"Low","gaps":["Single Co-IP and epistasis rescue with limited mechanistic resolution","Mechanism linking NUP37 to PI3K/AKT activation not defined","Direct binding not independently confirmed"]},{"year":2024,"claim":"Identified the post-translational control of NUP37 stability — TRIM28-mediated SUMOylation antagonizes ubiquitin-driven degradation.","evidence":"Reciprocal Co-IP, site-specific SUMOylation mutagenesis (K114/118/246), ubiquitination assays, xenografts in HCC","pmids":["39294431"],"confidence":"Medium","gaps":["E3 ligase responsible for K27-linked ubiquitination not identified","Whether SUMOylation affects NUP37's pore-assembly function unknown","Single-lab study"]},{"year":2024,"claim":"Linked NUP37 to DNA methylation machinery, positioning it upstream of DNMT1 to drive glioma proliferation and invasion.","evidence":"Co-IP and DNMT1-overexpression rescue of NUP37 depletion in glioma cells","pmids":["39174498"],"confidence":"Low","gaps":["Single Co-IP and epistasis rescue with limited mechanistic detail","Mechanism by which NUP37 controls DNMT1 not defined","Direct interaction not reciprocally validated"]},{"year":2026,"claim":"Defined a transcriptional input controlling NUP37 levels and tied NUP37 dosage to nuclear pore abundance and nuclear size during cell-fate conversion.","evidence":"ASCL1 promoter-binding assay, bidirectional knockdown/overexpression, live-cell imaging of nuclear size in neuronal transdifferentiation","pmids":["41759523"],"confidence":"Medium","gaps":["Mechanism coupling NUP37 dosage to NPC number and nuclear shrinkage not resolved","Generality beyond neuronal transdifferentiation untested","Single-study finding"]},{"year":null,"claim":"How NUP37's core structural role in the Y-complex mechanistically connects to its diverse signaling functions (YAP-TEAD, DNMT1, PI3K/AKT) and to its stability regulation remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unified model linking nuclear-pore function to oncogenic signaling roles","Direct vs nucleoporin-scaffold-mediated nature of signaling interactions undefined","Human structural data on the full Y-complex context for NUP37 not available in corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,5]}],"pathway":[],"complexes":["Y-complex (nuclear pore complex)"],"partners":["NUP160","ELYS","YAP1","TRIM28","DNMT1","DEPDC1B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8NFH4","full_name":"Nucleoporin Nup37","aliases":["Nup107-160 subcomplex subunit Nup37"],"length_aa":326,"mass_kda":36.7,"function":"Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation","subcellular_location":"Chromosome, centromere, kinetochore; Nucleus, nuclear pore complex","url":"https://www.uniprot.org/uniprotkb/Q8NFH4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP37","classification":"Not Classified","n_dependent_lines":134,"n_total_lines":1208,"dependency_fraction":0.11092715231788079},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CLIP1","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"SEC13","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP37","total_profiled":1310},"omim":[{"mim_id":"618348","title":"GALLOWAY-MOWAT SYNDROME 7; GAMOS7","url":"https://www.omim.org/entry/618348"},{"mim_id":"618179","title":"MICROCEPHALY 24, PRIMARY, AUTOSOMAL RECESSIVE; MCPH24","url":"https://www.omim.org/entry/618179"},{"mim_id":"609264","title":"NUCLEOPORIN, 37-KD; NUP37","url":"https://www.omim.org/entry/609264"},{"mim_id":"609263","title":"SEH1-LIKE PROTEIN; SEH1L","url":"https://www.omim.org/entry/609263"},{"mim_id":"608141","title":"NUCLEOPORIN, 43-KD; NUP43","url":"https://www.omim.org/entry/608141"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP37"},"hgnc":{"alias_symbol":["MGC5585","FLJ22618"],"prev_symbol":[]},"alphafold":{"accession":"Q8NFH4","domains":[{"cath_id":"2.130.10.10","chopping":"1-121_295-326","consensus_level":"medium","plddt":91.0935,"start":1,"end":326},{"cath_id":"2.130.10.10","chopping":"125-248","consensus_level":"medium","plddt":95.9443,"start":125,"end":248}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NFH4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NFH4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8NFH4-F1-predicted_aligned_error_v6.png","plddt_mean":92.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP37","jax_strain_url":"https://www.jax.org/strain/search?query=NUP37"},"sequence":{"accession":"Q8NFH4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8NFH4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8NFH4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8NFH4"}},"corpus_meta":[{"pmid":"22955883","id":"PMC_22955883","title":"Molecular basis for Nup37 and ELY5/ELYS recruitment to the nuclear pore complex.","date":"2012","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/22955883","citation_count":62,"is_preprint":false},{"pmid":"29228669","id":"PMC_29228669","title":"NUP37, a positive regulator of YAP/TEAD signaling, promotes the progression of hepatocellular carcinoma.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29228669","citation_count":25,"is_preprint":false},{"pmid":"32014308","id":"PMC_32014308","title":"NUP37 silencing induces inhibition of cell proliferation, G1 phase cell cycle arrest and apoptosis in non-small cell lung cancer cells.","date":"2020","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/32014308","citation_count":19,"is_preprint":false},{"pmid":"34386417","id":"PMC_34386417","title":"Evaluation of Oncogene NUP37 as a Potential Novel Biomarker in Breast Cancer.","date":"2021","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34386417","citation_count":11,"is_preprint":false},{"pmid":"37203403","id":"PMC_37203403","title":"DEPDC1B is involved in the proliferation, metastasis, cell cycle arrest and apoptosis of colon cancer cells by regulating NUP37.","date":"2023","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/37203403","citation_count":9,"is_preprint":false},{"pmid":"39294431","id":"PMC_39294431","title":"NUP37 accumulation mediated by TRIM28 enhances lipid synthesis to accelerate HCC progression.","date":"2024","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/39294431","citation_count":8,"is_preprint":false},{"pmid":"39174498","id":"PMC_39174498","title":"NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation.","date":"2024","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/39174498","citation_count":4,"is_preprint":false},{"pmid":"41759523","id":"PMC_41759523","title":"ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37.","date":"2026","source":"Stem cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41759523","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5595,"output_tokens":1651,"usd":0.020775,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8422,"output_tokens":2359,"usd":0.050542,"stage2_stop_reason":"end_turn"},"total_usd":0.071317,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"Crystal structure of S. pombe Nup37 in complex with Nup120 (a 174-kDa subassembly forming one short arm of the Y-complex) shows that Nup37 binds near the bend of the L-shaped Nup120 protein, potentially stabilizing the relative orientation of its two domains; reconstitution assays pinpointed residues crucial for this interaction; in vivo and in vitro results showed ELY5/ELYS binds near the Nup120-Nup37 interface; both Nup37 and ELY5 integrate directly via Nup120/160 into the heptameric Y-complex.\",\n      \"method\": \"X-ray crystallography, reconstitution assays, in vitro binding assays, cell biological experiments\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with reconstitution assays and mutagenesis in a single rigorous study, with both in vitro and in vivo validation\",\n      \"pmids\": [\"22955883\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NUP37 interacts with YAP protein and enhances the interaction between YAP and TEAD, thereby activating YAP/TEAD transcriptional signaling; knockdown of NUP37 inhibited HCC cell growth, migration, invasion, and metastasis.\",\n      \"method\": \"Co-immunoprecipitation, overexpression and knockdown experiments, cell growth/migration/invasion assays, in vivo mouse model\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP interaction and functional knockdown/overexpression with multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"29228669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TRIM28 was identified as an interacting protein of NUP37 and upregulates NUP37 protein levels; TRIM28-mediated SUMOylation of NUP37 at Lys114/118/246 inhibits K27-linked polyubiquitination of NUP37, thereby blocking its proteasomal degradation and increasing NUP37 protein stability, which promotes lipid synthesis and HCC progression.\",\n      \"method\": \"Co-immunoprecipitation, western blotting, mutagenesis (SUMOylation site identification), ubiquitination assays, xenograft mouse models\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus site-specific mutagenesis and ubiquitination assays in a single lab study\",\n      \"pmids\": [\"39294431\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NUP37 interacts with DNMT1 and promotes proliferation and invasion of glioma cells through this interaction; overexpression of DNMT1 rescued the adverse effects caused by NUP37 depletion, placing NUP37 upstream of DNMT1-mediated DNA methylation in glioma.\",\n      \"method\": \"Co-immunoprecipitation, knockdown/overexpression experiments, cell proliferation and invasion assays\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP interaction and epistasis rescue experiment reported in a single lab with limited mechanistic detail in abstract\",\n      \"pmids\": [\"39174498\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B physically binds NUP37 (verified by co-immunoprecipitation) and acts upstream of NUP37; NUP37 overexpression reversed the inhibitory effects of DEPDC1B silencing on CRC cell proliferation, migration, invasion, and PI3K/AKT signaling, placing NUP37 downstream of DEPDC1B in this pathway.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, overexpression rescue, flow cytometry, western blotting, in vivo xenograft\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and epistasis rescue, single lab, limited mechanistic resolution in abstract\",\n      \"pmids\": [\"37203403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ASCL1 directly binds the NUP37 promoter and suppresses NUP37 transcription; NUP37 knockdown enhanced ASCL1/miR124/p53shRNA-mediated transdifferentiation and nuclear shrinkage, while NUP37 overexpression had the opposite effect, establishing NUP37 as a regulator of nuclear pore complex abundance and nuclear size during neuronal conversion.\",\n      \"method\": \"Chromatin binding assay (ASCL1 promoter binding), knockdown and overexpression experiments, live-cell imaging of nuclear size during transdifferentiation\",\n      \"journal\": \"Stem cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct promoter binding plus bidirectional genetic manipulation (KD and OE) with quantitative nuclear size phenotype in a single study\",\n      \"pmids\": [\"41759523\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP37 is a nucleoporin that integrates into the heptameric Y-complex by binding directly to Nup120/160 (structurally defined by crystal structure and reconstitution), regulates nuclear pore complex abundance and thereby nuclear size (suppressed transcriptionally by ASCL1), interacts with YAP to enhance YAP-TEAD signaling, is stabilized post-translationally by TRIM28-mediated SUMOylation at Lys114/118/246 that blocks K27-polyubiquitination and proteasomal degradation, and promotes tumor cell proliferation and invasion in multiple cancers through interactions with DNMT1 and downstream of DEPDC1B via PI3K/AKT signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP37 is a structural nucleoporin that integrates directly into the heptameric Y-complex of the nuclear pore through binding to Nup120/160, where it docks near the bend of the L-shaped Nup120 subunit and stabilizes the relative orientation of its two domains adjacent to the ELYS-binding interface [#0]. Beyond its architectural role, NUP37 governs nuclear pore complex abundance and thereby nuclear size, a function placed under transcriptional control by ASCL1, which directly binds the NUP37 promoter to repress its expression during neuronal transdifferentiation [#5]. NUP37 protein levels are further set post-translationally: TRIM28 binds NUP37 and SUMOylates it at Lys114/118/246, blocking K27-linked polyubiquitination and proteasomal degradation to stabilize the protein [#2]. In cancer contexts, NUP37 acts as a pro-tumorigenic effector, interacting with YAP to enhance YAP-TEAD transcriptional signaling and driving hepatocellular carcinoma growth, migration, and invasion [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established how NUP37 is built into the nuclear pore — defining it as a direct structural subunit of the Y-complex rather than a peripheral associate.\",\n      \"evidence\": \"X-ray crystallography of S. pombe Nup37-Nup120 subassembly with reconstitution and mutagenesis\",\n      \"pmids\": [\n        \"22955883\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure is from S. pombe; human Y-complex architecture not directly resolved here\",\n        \"Functional consequence of the Nup37-Nup120 interface for pore assembly in vivo not quantified\",\n        \"Does not address regulation of NUP37 abundance or its non-structural roles\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected NUP37 to oncogenic transcription by showing it physically enhances YAP-TEAD signaling, moving it beyond a purely architectural role.\",\n      \"evidence\": \"Co-IP, knockdown/overexpression, growth/migration/invasion assays and mouse model in HCC\",\n      \"pmids\": [\n        \"29228669\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct vs indirect nature of the NUP37-YAP interaction not structurally resolved\",\n        \"Whether this depends on NUP37's nuclear pore role is unclear\",\n        \"Single-lab finding without reciprocal validation\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Placed NUP37 as a downstream effector of DEPDC1B/PI3K-AKT signaling in colorectal cancer via physical binding and epistasis rescue.\",\n      \"evidence\": \"Co-IP, siRNA knockdown, overexpression rescue, xenograft in CRC\",\n      \"pmids\": [\n        \"37203403\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP and epistasis rescue with limited mechanistic resolution\",\n        \"Mechanism linking NUP37 to PI3K/AKT activation not defined\",\n        \"Direct binding not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified the post-translational control of NUP37 stability — TRIM28-mediated SUMOylation antagonizes ubiquitin-driven degradation.\",\n      \"evidence\": \"Reciprocal Co-IP, site-specific SUMOylation mutagenesis (K114/118/246), ubiquitination assays, xenografts in HCC\",\n      \"pmids\": [\n        \"39294431\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"E3 ligase responsible for K27-linked ubiquitination not identified\",\n        \"Whether SUMOylation affects NUP37's pore-assembly function unknown\",\n        \"Single-lab study\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked NUP37 to DNA methylation machinery, positioning it upstream of DNMT1 to drive glioma proliferation and invasion.\",\n      \"evidence\": \"Co-IP and DNMT1-overexpression rescue of NUP37 depletion in glioma cells\",\n      \"pmids\": [\n        \"39174498\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP and epistasis rescue with limited mechanistic detail\",\n        \"Mechanism by which NUP37 controls DNMT1 not defined\",\n        \"Direct interaction not reciprocally validated\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined a transcriptional input controlling NUP37 levels and tied NUP37 dosage to nuclear pore abundance and nuclear size during cell-fate conversion.\",\n      \"evidence\": \"ASCL1 promoter-binding assay, bidirectional knockdown/overexpression, live-cell imaging of nuclear size in neuronal transdifferentiation\",\n      \"pmids\": [\n        \"41759523\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism coupling NUP37 dosage to NPC number and nuclear shrinkage not resolved\",\n        \"Generality beyond neuronal transdifferentiation untested\",\n        \"Single-study finding\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUP37's core structural role in the Y-complex mechanistically connects to its diverse signaling functions (YAP-TEAD, DNMT1, PI3K/AKT) and to its stability regulation remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unified model linking nuclear-pore function to oncogenic signaling roles\",\n        \"Direct vs nucleoporin-scaffold-mediated nature of signaling interactions undefined\",\n        \"Human structural data on the full Y-complex context for NUP37 not available in corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005635\",\n        \"supporting_discovery_ids\": [\n          0,\n          5\n        ]\n      }\n    ],\n    \"pathway\": [],\n    \"complexes\": [\n      \"Y-complex (nuclear pore complex)\"\n    ],\n    \"partners\": [\n      \"NUP160\",\n      \"ELYS\",\n      \"YAP1\",\n      \"TRIM28\",\n      \"DNMT1\",\n      \"DEPDC1B\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}