{"gene":"NUP37","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":2012,"finding":"Crystal structure of S. pombe Nup37 in complex with Nup120 reveals that Nup37 binds near the bend of the L-shaped Nup120 protein, stabilizing the relative orientation of its two domains and integrating into the heptameric Y-complex; ELY5/ELYS binds near the Nup120-Nup37 interface, as confirmed by reconstitution assays identifying key residues.","method":"X-ray crystallography, in vitro reconstitution assays, mutagenesis, in vivo/in vitro binding assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — crystal structure plus reconstitution and mutagenesis in a single rigorous study","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 in hepatocellular carcinoma cells.","method":"Co-immunoprecipitation, overexpression/knockdown with proliferation, migration and invasion assays","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 3 — single Co-IP with functional KD/OE phenotypes but no pathway reconstitution","pmids":["29228669"],"is_preprint":false},{"year":2023,"finding":"DEPDC1B physically interacts with NUP37 (confirmed by co-immunoprecipitation) and regulates PI3K/AKT signaling through NUP37; NUP37 overexpression rescues the growth-inhibitory effects of DEPDC1B silencing in colorectal cancer cells.","method":"Co-immunoprecipitation, epistasis rescue experiment (NUP37 OE + DEPDC1B KD), western blotting for PI3K/AKT pathway proteins","journal":"Molecular medicine reports","confidence":"Medium","confidence_rationale":"Tier 2/3 — reciprocal co-IP plus genetic epistasis rescue, single lab","pmids":["37203403"],"is_preprint":false},{"year":2024,"finding":"TRIM28 SUMOylates NUP37 at Lys114, Lys118, and Lys246, which inhibits K27-linked polyubiquitination and proteasomal degradation of NUP37, thereby increasing NUP37 protein stability and promoting lipid synthesis in hepatocellular carcinoma.","method":"Co-immunoprecipitation (TRIM28-NUP37 interaction), SUMOylation site mapping (Lys114/118/246), ubiquitination assay, knockdown with lipid synthesis and tumor growth readouts","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — site-specific PTM mapping with multiple orthogonal methods (SUMO, ubiquitin, stability assays) in one study","pmids":["39294431"],"is_preprint":false},{"year":2024,"finding":"NUP37 interacts with DNMT1 and promotes proliferation and invasion of glioma cells through DNMT1-mediated DNA methylation; DNMT1 overexpression rescues the defects caused by NUP37 depletion.","method":"Co-immunoprecipitation, NUP37 knockdown with proliferation/invasion assays, epistasis rescue by DNMT1 overexpression","journal":"Cell death discovery","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single Co-IP, partial mechanistic follow-up","pmids":["39174498"],"is_preprint":false},{"year":2026,"finding":"ASCL1 directly binds the NUP37 promoter to suppress NUP37 transcription, leading to reduced nuclear pore complex levels and nuclear shrinkage during transdifferentiation of fibroblasts to neurons; NUP37 knockdown enhances transdifferentiation and nuclear shrinkage, while NUP37 overexpression opposes these effects.","method":"Chromatin immunoprecipitation / promoter binding, NUP37 knockdown and overexpression with nuclear size and transdifferentiation readouts","journal":"Stem cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — direct promoter binding plus bidirectional genetic manipulation with defined cellular phenotype","pmids":["41759523"],"is_preprint":false}],"current_model":"NUP37 is a nucleoporin that integrates into the Y-complex of the nuclear pore complex by binding Nup120/Nup160 (structurally defined by crystallography and reconstitution); its protein stability is regulated by TRIM28-mediated SUMOylation (at Lys114/118/246) that prevents K27-linked ubiquitination and degradation; NUP37 interacts with YAP to enhance YAP–TEAD signaling, with DNMT1 to influence epigenetic gene regulation, and with DEPDC1B to modulate PI3K/AKT signaling; and its transcription is directly repressed by ASCL1 to control nuclear pore complex levels and nuclear size during neuronal differentiation."},"narrative":{"teleology":[{"year":2012,"claim":"Determining how Nup37 integrates into the Y-complex resolved a key architectural question: Nup37 binds the bend of Nup120, stabilizing inter-domain geometry and providing a composite surface for ELYS recruitment.","evidence":"X-ray crystallography of S. pombe Nup37–Nup120 complex with in vitro reconstitution and mutagenesis","pmids":["22955883"],"confidence":"High","gaps":["Structure determined in S. pombe; human Nup37–Nup160 interface not crystallized","How Nup37 contributes to overall NPC assembly dynamics in vivo remains unresolved","No structure for the full Y-complex heptamer with Nup37 in place"]},{"year":2017,"claim":"The discovery that NUP37 interacts with YAP and enhances YAP–TEAD binding established that NUP37 has signaling functions independent of its canonical role as a nucleoporin scaffold.","evidence":"Co-immunoprecipitation and knockdown/overexpression with proliferation, migration, and invasion assays in hepatocellular carcinoma cells","pmids":["29228669"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation or domain mapping for the NUP37–YAP interface","Whether the interaction occurs at the NPC or in the nucleoplasm/cytosol is unknown","No reconstitution of a NUP37–YAP–TEAD ternary complex"]},{"year":2023,"claim":"Identifying DEPDC1B as a physical partner of NUP37 that signals through PI3K/AKT expanded the repertoire of NUP37-mediated signaling pathways and showed epistatic dependence of DEPDC1B on NUP37.","evidence":"Co-immunoprecipitation and epistasis rescue (NUP37 overexpression rescuing DEPDC1B knockdown) with PI3K/AKT pathway western blots in colorectal cancer cells","pmids":["37203403"],"confidence":"Medium","gaps":["Direct versus indirect nature of the NUP37–PI3K/AKT link is unresolved","No identification of the NUP37 domain mediating DEPDC1B binding","Single-lab finding not independently replicated"]},{"year":2024,"claim":"Demonstrating TRIM28-mediated SUMOylation at specific lysines that antagonizes K27-linked ubiquitination resolved how NUP37 protein levels are post-translationally regulated, linking NUP37 stability to lipid metabolism in hepatocellular carcinoma.","evidence":"SUMOylation site mapping (Lys114/118/246), ubiquitination assays, stability measurements, and TRIM28 knockdown with lipid synthesis and tumor growth readouts","pmids":["39294431"],"confidence":"Medium","gaps":["The E3 ubiquitin ligase responsible for K27-linked polyubiquitination of NUP37 is unidentified","Whether SUMOylation of NUP37 affects its incorporation into the NPC is untested","Mechanism linking NUP37 protein levels to lipid biosynthesis gene expression is unclear"]},{"year":2024,"claim":"Finding that NUP37 interacts with DNMT1 and that DNMT1 overexpression rescues NUP37-depletion phenotypes suggested a role for NUP37 in epigenetic regulation through DNA methylation.","evidence":"Co-immunoprecipitation and epistasis rescue in glioma cell lines with proliferation and invasion assays","pmids":["39174498"],"confidence":"Low","gaps":["Single Co-IP in one lab without reciprocal validation or domain mapping","No identification of specific genomic loci whose methylation depends on the NUP37–DNMT1 interaction","Whether NUP37 directly modulates DNMT1 enzymatic activity or simply scaffolds it is unknown"]},{"year":2026,"claim":"Showing that ASCL1 directly represses NUP37 transcription to reduce NPC density and nuclear size during neuronal differentiation established NUP37 as a transcriptional target linking cell-fate determination to nuclear architecture.","evidence":"ChIP demonstrating ASCL1 binding at NUP37 promoter, bidirectional genetic manipulation (knockdown and overexpression) with nuclear size and transdifferentiation readouts in fibroblast-to-neuron conversion","pmids":["41759523"],"confidence":"Medium","gaps":["Whether NUP37 repression affects NPC composition globally or selectively is unexplored","The downstream gene-transport consequences of reduced NUP37/NPC levels in neurons are undefined","Whether other Y-complex subunits are co-regulated by ASCL1 is not addressed"]},{"year":null,"claim":"A unified model explaining how NUP37's structural role at the NPC relates to its multiple non-canonical signaling interactions (YAP, DEPDC1B, DNMT1) — whether these occur at the pore or via a free cytoplasmic/nuclear pool — remains unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No quantification of NPC-incorporated versus free NUP37 pools","No structural data for human NUP37 in complex with any signaling partner","No loss-of-function genetics in animal models to define physiological versus cancer-context roles"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,5]}],"pathway":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"complexes":["Nup107-160 complex (Y-complex)"],"partners":["NUP120/NUP160","ELYS","YAP","TEAD","DEPDC1B","TRIM28","DNMT1","ASCL1"],"other_free_text":[]},"mechanistic_narrative":"NUP37 is a structural nucleoporin of the Y-complex (Nup107-160 complex) of the nuclear pore complex, with additional signaling roles beyond nucleocytoplasmic transport. Crystallography of the S. pombe orthologue shows that Nup37 binds near the bend of the L-shaped Nup120/Nup160, stabilizing the relative orientation of its two domains and providing a docking interface for ELYS [PMID:22955883]. Beyond its structural role, NUP37 interacts with YAP to enhance YAP–TEAD transcriptional signaling [PMID:29228669], with DEPDC1B to modulate PI3K/AKT signaling [PMID:37203403], and with DNMT1 to influence DNA methylation-dependent gene regulation [PMID:39174498]; its protein stability is controlled by TRIM28-mediated SUMOylation at Lys114/118/246, which prevents K27-linked ubiquitination and proteasomal degradation [PMID:39294431]. NUP37 transcription is directly repressed by ASCL1 during neuronal differentiation, thereby reducing nuclear pore complex levels and nuclear size [PMID:41759523]."},"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":7,"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":3,"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":4831,"output_tokens":1499,"usd":0.018489},"stage2":{"model":"claude-opus-4-6","input_tokens":4737,"output_tokens":4247,"usd":0.19479},"total_usd":0.213279,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","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 reveals that Nup37 binds near the bend of the L-shaped Nup120 protein, stabilizing the relative orientation of its two domains and integrating into the heptameric Y-complex; ELY5/ELYS binds near the Nup120-Nup37 interface, as confirmed by reconstitution assays identifying key residues.\",\n      \"method\": \"X-ray crystallography, in vitro reconstitution assays, mutagenesis, in vivo/in vitro binding assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus reconstitution and mutagenesis in a single rigorous study\",\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 in hepatocellular carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, overexpression/knockdown with proliferation, migration and invasion assays\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP with functional KD/OE phenotypes but no pathway reconstitution\",\n      \"pmids\": [\"29228669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DEPDC1B physically interacts with NUP37 (confirmed by co-immunoprecipitation) and regulates PI3K/AKT signaling through NUP37; NUP37 overexpression rescues the growth-inhibitory effects of DEPDC1B silencing in colorectal cancer cells.\",\n      \"method\": \"Co-immunoprecipitation, epistasis rescue experiment (NUP37 OE + DEPDC1B KD), western blotting for PI3K/AKT pathway proteins\",\n      \"journal\": \"Molecular medicine reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — reciprocal co-IP plus genetic epistasis rescue, single lab\",\n      \"pmids\": [\"37203403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TRIM28 SUMOylates NUP37 at Lys114, Lys118, and Lys246, which inhibits K27-linked polyubiquitination and proteasomal degradation of NUP37, thereby increasing NUP37 protein stability and promoting lipid synthesis in hepatocellular carcinoma.\",\n      \"method\": \"Co-immunoprecipitation (TRIM28-NUP37 interaction), SUMOylation site mapping (Lys114/118/246), ubiquitination assay, knockdown with lipid synthesis and tumor growth readouts\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — site-specific PTM mapping with multiple orthogonal methods (SUMO, ubiquitin, stability assays) in one 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 DNMT1-mediated DNA methylation; DNMT1 overexpression rescues the defects caused by NUP37 depletion.\",\n      \"method\": \"Co-immunoprecipitation, NUP37 knockdown with proliferation/invasion assays, epistasis rescue by DNMT1 overexpression\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single Co-IP, partial mechanistic follow-up\",\n      \"pmids\": [\"39174498\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ASCL1 directly binds the NUP37 promoter to suppress NUP37 transcription, leading to reduced nuclear pore complex levels and nuclear shrinkage during transdifferentiation of fibroblasts to neurons; NUP37 knockdown enhances transdifferentiation and nuclear shrinkage, while NUP37 overexpression opposes these effects.\",\n      \"method\": \"Chromatin immunoprecipitation / promoter binding, NUP37 knockdown and overexpression with nuclear size and transdifferentiation readouts\",\n      \"journal\": \"Stem cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct promoter binding plus bidirectional genetic manipulation with defined cellular phenotype\",\n      \"pmids\": [\"41759523\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP37 is a nucleoporin that integrates into the Y-complex of the nuclear pore complex by binding Nup120/Nup160 (structurally defined by crystallography and reconstitution); its protein stability is regulated by TRIM28-mediated SUMOylation (at Lys114/118/246) that prevents K27-linked ubiquitination and degradation; NUP37 interacts with YAP to enhance YAP–TEAD signaling, with DNMT1 to influence epigenetic gene regulation, and with DEPDC1B to modulate PI3K/AKT signaling; and its transcription is directly repressed by ASCL1 to control nuclear pore complex levels and nuclear size during neuronal differentiation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP37 is a structural nucleoporin of the Y-complex (Nup107-160 complex) of the nuclear pore complex, with additional signaling roles beyond nucleocytoplasmic transport. Crystallography of the S. pombe orthologue shows that Nup37 binds near the bend of the L-shaped Nup120/Nup160, stabilizing the relative orientation of its two domains and providing a docking interface for ELYS [PMID:22955883]. Beyond its structural role, NUP37 interacts with YAP to enhance YAP–TEAD transcriptional signaling [PMID:29228669], with DEPDC1B to modulate PI3K/AKT signaling [PMID:37203403], and with DNMT1 to influence DNA methylation-dependent gene regulation [PMID:39174498]; its protein stability is controlled by TRIM28-mediated SUMOylation at Lys114/118/246, which prevents K27-linked ubiquitination and proteasomal degradation [PMID:39294431]. NUP37 transcription is directly repressed by ASCL1 during neuronal differentiation, thereby reducing nuclear pore complex levels and nuclear size [PMID:41759523].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Determining how Nup37 integrates into the Y-complex resolved a key architectural question: Nup37 binds the bend of Nup120, stabilizing inter-domain geometry and providing a composite surface for ELYS recruitment.\",\n      \"evidence\": \"X-ray crystallography of S. pombe Nup37–Nup120 complex with in vitro reconstitution and mutagenesis\",\n      \"pmids\": [\"22955883\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure determined in S. pombe; human Nup37–Nup160 interface not crystallized\",\n        \"How Nup37 contributes to overall NPC assembly dynamics in vivo remains unresolved\",\n        \"No structure for the full Y-complex heptamer with Nup37 in place\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The discovery that NUP37 interacts with YAP and enhances YAP–TEAD binding established that NUP37 has signaling functions independent of its canonical role as a nucleoporin scaffold.\",\n      \"evidence\": \"Co-immunoprecipitation and knockdown/overexpression with proliferation, migration, and invasion assays in hepatocellular carcinoma cells\",\n      \"pmids\": [\"29228669\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation or domain mapping for the NUP37–YAP interface\",\n        \"Whether the interaction occurs at the NPC or in the nucleoplasm/cytosol is unknown\",\n        \"No reconstitution of a NUP37–YAP–TEAD ternary complex\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying DEPDC1B as a physical partner of NUP37 that signals through PI3K/AKT expanded the repertoire of NUP37-mediated signaling pathways and showed epistatic dependence of DEPDC1B on NUP37.\",\n      \"evidence\": \"Co-immunoprecipitation and epistasis rescue (NUP37 overexpression rescuing DEPDC1B knockdown) with PI3K/AKT pathway western blots in colorectal cancer cells\",\n      \"pmids\": [\"37203403\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect nature of the NUP37–PI3K/AKT link is unresolved\",\n        \"No identification of the NUP37 domain mediating DEPDC1B binding\",\n        \"Single-lab finding not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrating TRIM28-mediated SUMOylation at specific lysines that antagonizes K27-linked ubiquitination resolved how NUP37 protein levels are post-translationally regulated, linking NUP37 stability to lipid metabolism in hepatocellular carcinoma.\",\n      \"evidence\": \"SUMOylation site mapping (Lys114/118/246), ubiquitination assays, stability measurements, and TRIM28 knockdown with lipid synthesis and tumor growth readouts\",\n      \"pmids\": [\"39294431\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The E3 ubiquitin ligase responsible for K27-linked polyubiquitination of NUP37 is unidentified\",\n        \"Whether SUMOylation of NUP37 affects its incorporation into the NPC is untested\",\n        \"Mechanism linking NUP37 protein levels to lipid biosynthesis gene expression is unclear\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Finding that NUP37 interacts with DNMT1 and that DNMT1 overexpression rescues NUP37-depletion phenotypes suggested a role for NUP37 in epigenetic regulation through DNA methylation.\",\n      \"evidence\": \"Co-immunoprecipitation and epistasis rescue in glioma cell lines with proliferation and invasion assays\",\n      \"pmids\": [\"39174498\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP in one lab without reciprocal validation or domain mapping\",\n        \"No identification of specific genomic loci whose methylation depends on the NUP37–DNMT1 interaction\",\n        \"Whether NUP37 directly modulates DNMT1 enzymatic activity or simply scaffolds it is unknown\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Showing that ASCL1 directly represses NUP37 transcription to reduce NPC density and nuclear size during neuronal differentiation established NUP37 as a transcriptional target linking cell-fate determination to nuclear architecture.\",\n      \"evidence\": \"ChIP demonstrating ASCL1 binding at NUP37 promoter, bidirectional genetic manipulation (knockdown and overexpression) with nuclear size and transdifferentiation readouts in fibroblast-to-neuron conversion\",\n      \"pmids\": [\"41759523\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NUP37 repression affects NPC composition globally or selectively is unexplored\",\n        \"The downstream gene-transport consequences of reduced NUP37/NPC levels in neurons are undefined\",\n        \"Whether other Y-complex subunits are co-regulated by ASCL1 is not addressed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unified model explaining how NUP37's structural role at the NPC relates to its multiple non-canonical signaling interactions (YAP, DEPDC1B, DNMT1) — whether these occur at the pore or via a free cytoplasmic/nuclear pool — remains unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No quantification of NPC-incorporated versus free NUP37 pools\",\n        \"No structural data for human NUP37 in complex with any signaling partner\",\n        \"No loss-of-function genetics in animal models to define physiological versus cancer-context roles\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"Nup107-160 complex (Y-complex)\"],\n    \"partners\": [\"NUP120/NUP160\", \"ELYS\", \"YAP\", \"TEAD\", \"DEPDC1B\", \"TRIM28\", \"DNMT1\", \"ASCL1\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway field - it should use Reactome term_ids, not GO terms. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"NUP37 is a structural nucleoporin of the Y-complex (Nup107-160 complex) of the nuclear pore complex, with additional signaling roles beyond nucleocytoplasmic transport. Crystallography of the S. pombe orthologue shows that Nup37 binds near the bend of the L-shaped Nup120/Nup160, stabilizing the relative orientation of its two domains and providing a docking interface for ELYS [PMID:22955883]. Beyond its structural role, NUP37 interacts with YAP to enhance YAP–TEAD transcriptional signaling [PMID:29228669], with DEPDC1B to modulate PI3K/AKT signaling [PMID:37203403], and with DNMT1 to influence DNA methylation-dependent gene regulation [PMID:39174498]; its protein stability is controlled by TRIM28-mediated SUMOylation at Lys114/118/246, which prevents K27-linked ubiquitination and proteasomal degradation [PMID:39294431]. NUP37 transcription is directly repressed by ASCL1 during neuronal differentiation, thereby reducing nuclear pore complex levels and nuclear size [PMID:41759523].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Determining how Nup37 integrates into the Y-complex resolved a key architectural question: Nup37 binds the bend of Nup120, stabilizing inter-domain geometry and providing a composite surface for ELYS recruitment.\",\n      \"evidence\": \"X-ray crystallography of S. pombe Nup37–Nup120 complex with in vitro reconstitution and mutagenesis\",\n      \"pmids\": [\"22955883\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure determined in S. pombe; human Nup37–Nup160 interface not crystallized\",\n        \"How Nup37 contributes to overall NPC assembly dynamics in vivo remains unresolved\",\n        \"No structure for the full Y-complex heptamer with Nup37 in place\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The discovery that NUP37 interacts with YAP and enhances YAP–TEAD binding established that NUP37 has signaling functions independent of its canonical role as a nucleoporin scaffold.\",\n      \"evidence\": \"Co-immunoprecipitation and knockdown/overexpression with proliferation, migration, and invasion assays in hepatocellular carcinoma cells\",\n      \"pmids\": [\"29228669\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation or domain mapping for the NUP37–YAP interface\",\n        \"Whether the interaction occurs at the NPC or in the nucleoplasm/cytosol is unknown\",\n        \"No reconstitution of a NUP37–YAP–TEAD ternary complex\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying DEPDC1B as a physical partner of NUP37 that signals through PI3K/AKT expanded the repertoire of NUP37-mediated signaling pathways and showed epistatic dependence of DEPDC1B on NUP37.\",\n      \"evidence\": \"Co-immunoprecipitation and epistasis rescue (NUP37 overexpression rescuing DEPDC1B knockdown) with PI3K/AKT pathway western blots in colorectal cancer cells\",\n      \"pmids\": [\"37203403\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect nature of the NUP37–PI3K/AKT link is unresolved\",\n        \"No identification of the NUP37 domain mediating DEPDC1B binding\",\n        \"Single-lab finding not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrating TRIM28-mediated SUMOylation at specific lysines that antagonizes K27-linked ubiquitination resolved how NUP37 protein levels are post-translationally regulated, linking NUP37 stability to lipid metabolism in hepatocellular carcinoma.\",\n      \"evidence\": \"SUMOylation site mapping (Lys114/118/246), ubiquitination assays, stability measurements, and TRIM28 knockdown with lipid synthesis and tumor growth readouts\",\n      \"pmids\": [\"39294431\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The E3 ubiquitin ligase responsible for K27-linked polyubiquitination of NUP37 is unidentified\",\n        \"Whether SUMOylation of NUP37 affects its incorporation into the NPC is untested\",\n        \"Mechanism linking NUP37 protein levels to lipid biosynthesis gene expression is unclear\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Finding that NUP37 interacts with DNMT1 and that DNMT1 overexpression rescues NUP37-depletion phenotypes suggested a role for NUP37 in epigenetic regulation through DNA methylation.\",\n      \"evidence\": \"Co-immunoprecipitation and epistasis rescue in glioma cell lines with proliferation and invasion assays\",\n      \"pmids\": [\"39174498\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP in one lab without reciprocal validation or domain mapping\",\n        \"No identification of specific genomic loci whose methylation depends on the NUP37–DNMT1 interaction\",\n        \"Whether NUP37 directly modulates DNMT1 enzymatic activity or simply scaffolds it is unknown\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Showing that ASCL1 directly represses NUP37 transcription to reduce NPC density and nuclear size during neuronal differentiation established NUP37 as a transcriptional target linking cell-fate determination to nuclear architecture.\",\n      \"evidence\": \"ChIP demonstrating ASCL1 binding at NUP37 promoter, bidirectional genetic manipulation (knockdown and overexpression) with nuclear size and transdifferentiation readouts in fibroblast-to-neuron conversion\",\n      \"pmids\": [\"41759523\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether NUP37 repression affects NPC composition globally or selectively is unexplored\",\n        \"The downstream gene-transport consequences of reduced NUP37/NPC levels in neurons are undefined\",\n        \"Whether other Y-complex subunits are co-regulated by ASCL1 is not addressed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unified model explaining how NUP37's structural role at the NPC relates to its multiple non-canonical signaling interactions (YAP, DEPDC1B, DNMT1) — whether these occur at the pore or via a free cytoplasmic/nuclear pool — remains unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No quantification of NPC-incorporated versus free NUP37 pools\",\n        \"No structural data for human NUP37 in complex with any signaling partner\",\n        \"No loss-of-function genetics in animal models to define physiological versus cancer-context roles\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\"Nup107-160 complex (Y-complex)\"],\n    \"partners\": [\"NUP120/NUP160\", \"ELYS\", \"YAP\", \"DEPDC1B\", \"TRIM28\", \"DNMT1\", \"ASCL1\"],\n    \"other_free_text\": []\n  }\n}\n```"}