{"gene":"NUP88","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1997,"finding":"Nup88 is a novel nuclear pore complex (NPC) component that localizes to the NPC in a CAN/Nup214-dependent manner; depletion of CAN from the NPC results in concomitant loss of Nup88, establishing that Nup88 NPC localization depends on its interaction with CAN/Nup214. Human CRM1 was identified as part of a dynamic subcomplex with CAN/Nup214 and Nup88.","method":"Co-immunoprecipitation, immunofluorescence, CAN depletion experiments, overexpression of FG-repeat domain of CAN in cells","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction and depletion experiments with clear functional consequence, foundational paper with 410 citations","pmids":["9049309"],"is_preprint":false},{"year":2004,"finding":"Nup88 localizes midway between Nup358 and Nup214 on the cytoplasmic face of the NPC and physically interacts with both. RNAi of Nup88 or Nup214 strongly reduces Nup358 at the nuclear envelope, demonstrating that Nup88 and Nup214 together mediate attachment of Nup358 to the NPC. Nup88 and Nup214 show mutual interdependence at the NPC and are not affected by absence of Nup358.","method":"RNA interference, immunofluorescence, co-immunoprecipitation, electron microscopy","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal RNAi with clear localization phenotype and Co-IP interaction data, multiple orthogonal methods","pmids":["14993277"],"is_preprint":false},{"year":2006,"finding":"The Nup214-Nup88 subcomplex is specifically required for CRM1-mediated nuclear export of the 60S preribosomal subunit via the adaptor NMD3. RNAi depletion of Nup214-Nup88 caused dramatic defects in 60S preribsosome export but only minor defects in other CRM1 cargoes. The coiled-coil region of Nup214 (coinciding with Nup88 recruitment to the NPC) is sufficient for 60S nuclear export, while the FG-repeat domain is dispensable for this function.","method":"RNA interference, nuclear export assays, Nup214 domain deletion constructs, fluorescence microscopy","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — RNAi with specific export assay readout and domain rescue experiments, multiple orthogonal approaches","pmids":["16675447"],"is_preprint":false},{"year":2011,"finding":"Nup88 directly binds lamin A in vitro and in vivo. The interaction is mediated by the N-terminus of Nup88, which specifically binds the tail domain of lamin A but not lamins B1 or B2. Laminopathy-associated lamin A mutants disrupt the interaction with Nup88 in vitro. Immunoelectron microscopy revealed that Nup88 localizes to both the cytoplasmic and nuclear face of the NPC, suggesting a pool of nuclear-face Nup88 provides a binding site for lamin A.","method":"In vitro binding assays, co-immunoprecipitation, immunofluorescence (epitope masking assay), immunoelectron microscopy in Xenopus oocytes, domain mapping","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro reconstitution plus in vivo Co-IP and structural localization, multiple orthogonal methods","pmids":["21289091"],"is_preprint":false},{"year":2016,"finding":"NUP88 overexpression sequesters NUP98-RAE1 away from APC/C-CDH1, thereby triggering premitotic proteolysis of PLK1 (polo-like kinase 1). Loss of PLK1 disrupts centrosome separation, causes mitotic spindle asymmetry, merotelic microtubule-kinetochore attachments, lagging chromosomes, and aneuploidy. NUP88 thus functions in a NUP88-NUP98-RAE1-APC/C-CDH1 axis that regulates mitotic entry.","method":"Transgenic mouse overexpression, co-immunoprecipitation, Western blotting, live-cell imaging, chromosomal instability assays, PLK1 insufficiency rescue experiments","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1-2 — in vivo mouse model plus Co-IP and rescue experiments, multiple orthogonal methods with strong mechanistic follow-up","pmids":["26731471"],"is_preprint":false},{"year":2008,"finding":"Nup88 is upregulated by hypertonic stress in kidney (IMCD3) cells and acts to retain the transcription factor TonEBP in the nucleus. Silencing Nup88 under hypertonic conditions reduces nuclear retention of TonEBP, blunts transcription of osmoprotective target genes, and reduces cell viability. Under isotonic conditions, nuclear export of TonEBP involves CRM1, but under hypertonic stress the export is CRM1-independent.","method":"Antibody microarray, Western blot, qPCR, siRNA knockdown, GFP-TonEBP nuclear retention assay, CRM1 inhibitor (leptomycin B) treatment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined transcriptional phenotype; single lab but multiple orthogonal methods","pmids":["18606815"],"is_preprint":false},{"year":2018,"finding":"NUP88 depletion in human and mouse cell lines and fetal muscle tissue affects rapsyn, a key regulator of the muscle nicotinic acetylcholine receptor at the neuromuscular junction. Genetic disruption of nup88 in zebrafish causes locomotor defects and neuromuscular junction defects, rescued by wild-type but not disease-mutant Nup88.","method":"siRNA knockdown in human/mouse cell lines, zebrafish nup88 morpholino/mutant analysis, immunohistochemistry, rescue experiments with wild-type vs. mutant Nup88","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function in multiple systems (cell lines and zebrafish) with rescue, but rapsyn link established mainly by immunostaining/Western blot rather than direct interaction assay","pmids":["30543681"],"is_preprint":false},{"year":2019,"finding":"Nup88 and its partner Nup214 negatively regulate Notch signaling. Loss of Nup88/Nup214 inhibits nuclear export of RBP-J (the DNA-binding component of the Notch pathway), causing increased RBP-J binding to cognate promoter regions and elevated downstream Notch signaling. This was demonstrated in mammalian cells and validated in zebrafish.","method":"Reporter gene assays, RNAi knockdown, immunocytochemistry, ChIP-qPCR, zebrafish in vivo validation","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (reporter, ChIP, ICC) plus in vivo zebrafish validation; single lab","pmids":["31186352"],"is_preprint":false},{"year":2023,"finding":"Nup88 interacts with Nup62 in a glycosylation-independent and cell-cycle-independent manner, and this interaction stabilizes overexpressed Nup88 by inhibiting proteasome-mediated degradation. Stabilized Nup88 interacts with NF-κB (p65) and sequesters p65 partly into the nucleus of unstimulated cells, inducing NF-κB target genes (Akt, c-Myc, IL-6, BIRC3).","method":"Co-immunoprecipitation, proteasome inhibitor assays, Western blotting, immunofluorescence, gene expression analysis","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 3 — Co-IP with functional follow-up; single lab with moderate mechanistic depth","pmids":["36845732"],"is_preprint":false},{"year":2021,"finding":"Overexpression of Nup88 in HeLa cells promotes cell migration and invasion through upregulation of matrix metalloproteinase-12 (MMP-12) at both mRNA and protein levels. Knockdown of Nup88 suppresses migration and invasion, and pharmacological inhibition of MMP-12 enzymatic activity suppresses Nup88-overexpression-induced invasion.","method":"Overexpression and RNAi knockdown, migration/invasion assays, RT-PCR, Western blot, MMP-12 inhibitor treatment","journal":"Histochemistry and cell biology","confidence":"Medium","confidence_rationale":"Tier 2-3 — loss- and gain-of-function with defined molecular output (MMP-12) and pharmacological rescue; single lab","pmids":["34331103"],"is_preprint":false},{"year":2016,"finding":"NUP88 overexpression blocks MISP (mitotic interactor and substrate of PLK1) phosphorylation, which is required for normal spindle formation and accurate chromosome segregation during mitosis. NUP88 was found to interact with MISP by proteomic/interactome analysis.","method":"Subcellular proteomic pulldown/interactome analysis, phosphorylation assays","journal":"Genes, chromosomes & cancer","confidence":"Low","confidence_rationale":"Tier 3 — single pulldown/proteomic identification with limited mechanistic follow-up; single lab","pmids":["27636375"],"is_preprint":false},{"year":2015,"finding":"Flightless I (FLII) interacts with Nup88 via its LRR domain, as demonstrated by GST pulldown and co-immunoprecipitation, suggesting FLII may participate in nuclear export through interaction with Nup88.","method":"GST pulldown, co-immunoprecipitation, domain deletion constructs","journal":"Sheng wu gong cheng xue bao = Chinese journal of biotechnology","confidence":"Low","confidence_rationale":"Tier 3 — single pulldown and Co-IP; no further functional validation of the interaction's consequence","pmids":["26762046"],"is_preprint":false}],"current_model":"NUP88 is a cytoplasmic-face nuclear pore complex component that depends on CAN/NUP214 for its NPC localization, physically scaffolds NUP358 and lamin A at the NPC, participates with NUP214 in CRM1-mediated 60S preribosomal export, regulates nuclear retention of transcription factors (NF-κB, TonEBP, RBP-J) by modulating their nuclear export, and when overexpressed sequesters the NUP98-RAE1 complex away from APC/C-CDH1 to trigger premitotic PLK1 degradation, thereby promoting chromosomal instability and aneuploidy."},"narrative":{"teleology":[{"year":1997,"claim":"Identifying NUP88 as an NPC component whose pore localization depends on CAN/NUP214 established the first molecular dependency in the cytoplasmic nucleoporin network and linked NUP88 to the CRM1 export machinery.","evidence":"Co-immunoprecipitation and CAN depletion experiments in human cells","pmids":["9049309"],"confidence":"High","gaps":["Stoichiometry of the NUP88–NUP214–CRM1 subcomplex unknown","Whether NUP88 contacts CRM1 directly or only via NUP214 unresolved"]},{"year":2004,"claim":"Demonstrating that NUP88 and NUP214 are both required for NUP358 attachment to the NPC revealed NUP88 as a structural scaffold of the cytoplasmic filament network, resolving how the outermost pore components are anchored.","evidence":"RNAi of NUP88/NUP214 with immunofluorescence and electron microscopy readouts","pmids":["14993277"],"confidence":"High","gaps":["Direct binding interface between NUP88 and NUP358 not mapped","Whether NUP88 loss affects NPC transport beyond NUP358-dependent pathways unclear"]},{"year":2006,"claim":"Showing that the NUP214–NUP88 subcomplex is specifically required for CRM1-mediated 60S preribosomal export—but largely dispensable for other CRM1 cargoes—revealed cargo selectivity at individual NPC subcomplexes.","evidence":"RNAi depletion coupled with specific nuclear export assays and NUP214 domain rescue constructs","pmids":["16675447"],"confidence":"High","gaps":["How NUP88 itself contributes to 60S selectivity versus serving only as a NUP214 anchor unresolved","Other potential cargo-specific export roles of NUP88 not surveyed"]},{"year":2008,"claim":"Finding that NUP88 upregulation under hypertonic stress retains TonEBP in the nucleus provided the first evidence that NUP88 levels modulate transcription factor localization in a physiological signaling context.","evidence":"siRNA knockdown in kidney IMCD3 cells with GFP-TonEBP nuclear retention assays and CRM1 inhibitor treatment","pmids":["18606815"],"confidence":"Medium","gaps":["Mechanism by which NUP88 retains TonEBP independently of CRM1 not defined","Whether NUP88 directly contacts TonEBP or acts indirectly unknown"]},{"year":2011,"claim":"Demonstrating direct NUP88–lamin A binding and showing disruption by laminopathy mutations expanded NUP88 function beyond the cytoplasmic face to a structural link between the NPC and the nuclear lamina.","evidence":"In vitro binding assays, co-immunoprecipitation, immunoelectron microscopy in Xenopus oocytes","pmids":["21289091"],"confidence":"High","gaps":["Functional consequence of NUP88–lamin A disruption on NPC integrity or transport not established","Whether loss of this interaction contributes to laminopathy phenotypes untested in vivo"]},{"year":2016,"claim":"Elucidating the NUP88→NUP98-RAE1→APC/C-CDH1→PLK1 axis explained how NUP88 overexpression causes chromosomal instability, providing a mechanistic link between nucleoporin dysregulation and aneuploidy in cancer.","evidence":"Transgenic NUP88-overexpressing mice, co-immunoprecipitation, live-cell imaging, PLK1 rescue experiments","pmids":["26731471"],"confidence":"High","gaps":["Whether endogenous NUP88 levels regulate PLK1 during normal mitosis unknown","Tissue-specific thresholds for NUP88 overexpression to induce CIN not determined"]},{"year":2018,"claim":"Linking NUP88 loss of function to neuromuscular junction defects via rapsyn dysregulation in zebrafish and mammalian cells expanded the gene's physiological roles to tissue-specific developmental processes.","evidence":"siRNA in human/mouse cells, zebrafish mutant analysis with wild-type vs. mutant rescue","pmids":["30543681"],"confidence":"Medium","gaps":["Whether NUP88 directly interacts with rapsyn or acts via nuclear transport of an upstream regulator unresolved","Specific NUP88 mutations found in patients not functionally characterized at the NPC level"]},{"year":2019,"claim":"Showing that NUP88/NUP214 loss inhibits nuclear export of RBP-J, thereby amplifying Notch signaling, revealed NUP88 as a negative regulator of a major developmental signaling pathway.","evidence":"Reporter assays, ChIP-qPCR, RNAi in mammalian cells, zebrafish validation","pmids":["31186352"],"confidence":"Medium","gaps":["Whether RBP-J export is CRM1-dependent through NUP88 or uses an alternative pathway not resolved","Physiological contexts where NUP88-mediated Notch regulation is rate-limiting unknown"]},{"year":2023,"claim":"Identifying NUP62 as a stabilizer of overexpressed NUP88 (by blocking proteasomal degradation) and showing that stabilized NUP88 sequesters NF-κB p65 in the nucleus clarified how NUP88 overexpression in tumors could constitutively activate NF-κB target genes.","evidence":"Co-immunoprecipitation, proteasome inhibitor assays, gene expression analysis in human cells","pmids":["36845732"],"confidence":"Medium","gaps":["Whether NUP88–p65 interaction is direct not determined","In vivo relevance of NUP62-dependent NUP88 stabilization in tumors not tested"]},{"year":null,"claim":"A unifying structural model of how NUP88 simultaneously scaffolds NUP214, NUP358, and lamin A at the NPC, and how its stoichiometric balance controls the switch between transport and mitotic regulation, remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of NUP88 in the context of the intact NPC subcomplex","Mechanism by which NUP88 selectively modulates export of specific transcription factors versus bulk CRM1 cargo unknown","Whether NUP88 overexpression-driven CIN and NF-κB activation operate through independent or convergent oncogenic pathways not determined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,5,7]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[4,10]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[2]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7,8]}],"complexes":["NUP88-NUP214 subcomplex","Nuclear pore complex (NPC)"],"partners":["NUP214","NUP358","LMNA","NUP98","RAE1","NUP62","CRM1"],"other_free_text":[]},"mechanistic_narrative":"NUP88 is a cytoplasmic-face nuclear pore complex (NPC) component that scaffolds NPC architecture, regulates selective nuclear export, and controls mitotic fidelity. Its NPC localization depends on CAN/NUP214, and together these nucleoporins mediate attachment of NUP358 to the pore and are specifically required for CRM1-dependent export of 60S preribosomal subunits [PMID:9049309, PMID:14993277, PMID:16675447]. NUP88 directly binds lamin A via its N-terminus and modulates nuclear retention of transcription factors including NF-κB, TonEBP, and RBP-J, thereby influencing Notch signaling and osmotic stress responses [PMID:21289091, PMID:18606815, PMID:31186352, PMID:36845732]. When overexpressed—a frequent event in tumors—NUP88 sequesters the NUP98–RAE1 complex away from APC/C-CDH1, causing premitotic PLK1 degradation, defective centrosome separation, and chromosomal instability [PMID:26731471]."},"prefetch_data":{"uniprot":{"accession":"Q99567","full_name":"Nuclear pore complex protein Nup88","aliases":["88 kDa nucleoporin","Nucleoporin Nup88"],"length_aa":741,"mass_kda":83.5,"function":"Component of nuclear pore complex","subcellular_location":"Nucleus, nuclear pore complex","url":"https://www.uniprot.org/uniprotkb/Q99567/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP88","classification":"Common Essential","n_dependent_lines":1192,"n_total_lines":1208,"dependency_fraction":0.9867549668874173},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NUP214","stoichiometry":10.0},{"gene":"DNAJC24","stoichiometry":0.2},{"gene":"FDPS","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"NUTF2","stoichiometry":0.2},{"gene":"PMVK","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"XPO1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP88","total_profiled":1310},"omim":[{"mim_id":"618426","title":"ENCEPHALOPATHY, ACUTE, INFECTION-INDUCED, SUSCEPTIBILITY TO, 9; IIAE9","url":"https://www.omim.org/entry/618426"},{"mim_id":"618393","title":"FETAL AKINESIA DEFORMATION SEQUENCE 4; FADS4","url":"https://www.omim.org/entry/618393"},{"mim_id":"611729","title":"KINESIN LIGHT CHAIN 2; KLC2","url":"https://www.omim.org/entry/611729"},{"mim_id":"602559","title":"EXPORTIN 1; XPO1","url":"https://www.omim.org/entry/602559"},{"mim_id":"602552","title":"NUCLEOPORIN, 88-KD; NUP88","url":"https://www.omim.org/entry/602552"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP88"},"hgnc":{"alias_symbol":["MGC8530"],"prev_symbol":[]},"alphafold":{"accession":"Q99567","domains":[{"cath_id":"-","chopping":"12-33_55-197","consensus_level":"medium","plddt":87.0199,"start":12,"end":197},{"cath_id":"-","chopping":"233-343_360-371","consensus_level":"medium","plddt":85.9322,"start":233,"end":371},{"cath_id":"-","chopping":"389-432_439-488_546-557","consensus_level":"medium","plddt":84.7964,"start":389,"end":557}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99567","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99567-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99567-F1-predicted_aligned_error_v6.png","plddt_mean":79.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP88","jax_strain_url":"https://www.jax.org/strain/search?query=NUP88"},"sequence":{"accession":"Q99567","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99567.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99567/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99567"}},"corpus_meta":[{"pmid":"9049309","id":"PMC_9049309","title":"The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.","date":"1997","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/9049309","citation_count":410,"is_preprint":false},{"pmid":"19700630","id":"PMC_19700630","title":"Nuclear pore complex component MOS7/Nup88 is required for innate immunity and nuclear accumulation of defense regulators in Arabidopsis.","date":"2009","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/19700630","citation_count":216,"is_preprint":false},{"pmid":"14993277","id":"PMC_14993277","title":"Nup358/RanBP2 attaches to the nuclear pore complex via association with Nup88 and Nup214/CAN and plays a supporting role in CRM1-mediated nuclear protein export.","date":"2004","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/14993277","citation_count":140,"is_preprint":false},{"pmid":"14999780","id":"PMC_14999780","title":"Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer.","date":"2004","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/14999780","citation_count":80,"is_preprint":false},{"pmid":"10554006","id":"PMC_10554006","title":"The nuclear pore complex protein Nup88 is overexpressed in tumor cells.","date":"1999","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/10554006","citation_count":72,"is_preprint":false},{"pmid":"16675447","id":"PMC_16675447","title":"Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16675447","citation_count":71,"is_preprint":false},{"pmid":"21289091","id":"PMC_21289091","title":"The nucleoporin Nup88 is interacting with nuclear lamin A.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21289091","citation_count":37,"is_preprint":false},{"pmid":"12063548","id":"PMC_12063548","title":"Expression of p16, p27, p53, p73 and Nup88 proteins in matched primary and metastatic melanoma cells.","date":"2002","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/12063548","citation_count":37,"is_preprint":false},{"pmid":"12759533","id":"PMC_12759533","title":"Clinicopathological significance of Nup88 expression in patients with colorectal cancer.","date":"2003","source":"Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/12759533","citation_count":34,"is_preprint":false},{"pmid":"26731471","id":"PMC_26731471","title":"Nuclear pore protein NUP88 activates anaphase-promoting complex to promote aneuploidy.","date":"2016","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/26731471","citation_count":33,"is_preprint":false},{"pmid":"30543681","id":"PMC_30543681","title":"Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence.","date":"2018","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30543681","citation_count":27,"is_preprint":false},{"pmid":"17264541","id":"PMC_17264541","title":"Nup88 expression in normal mucosa, adenoma, primary adenocarcinoma and lymph node metastasis in the colorectum.","date":"2007","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/17264541","citation_count":25,"is_preprint":false},{"pmid":"21327081","id":"PMC_21327081","title":"Nucleoporin MOS7/Nup88 contributes to plant immunity and nuclear accumulation of defense regulators.","date":"2010","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21327081","citation_count":22,"is_preprint":false},{"pmid":"25489100","id":"PMC_25489100","title":"Nucleoporin MOS7/Nup88 is required for mitosis in gametogenesis and seed development in Arabidopsis.","date":"2014","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25489100","citation_count":22,"is_preprint":false},{"pmid":"21863385","id":"PMC_21863385","title":"Increased serum level of Nup88 protein is associated with the development of colorectal cancer.","date":"2011","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21863385","citation_count":18,"is_preprint":false},{"pmid":"18606815","id":"PMC_18606815","title":"Nucleoporin 88 (Nup88) is regulated by hypertonic stress in kidney cells to retain the transcription factor tonicity enhancer-binding protein (TonEBP) in the nucleus.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18606815","citation_count":16,"is_preprint":false},{"pmid":"36845732","id":"PMC_36845732","title":"Overexpressed Nup88 stabilized through interaction with Nup62 promotes NF-κB dependent pathways in cancer.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36845732","citation_count":15,"is_preprint":false},{"pmid":"20973273","id":"PMC_20973273","title":"Nup88 expression is associated with myometrial invasion in endometrial carcinoma.","date":"2010","source":"International journal of gynecological cancer : official journal of the International Gynecological Cancer Society","url":"https://pubmed.ncbi.nlm.nih.gov/20973273","citation_count":13,"is_preprint":false},{"pmid":"16174445","id":"PMC_16174445","title":"Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro.","date":"2005","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/16174445","citation_count":12,"is_preprint":false},{"pmid":"34331103","id":"PMC_34331103","title":"Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells.","date":"2021","source":"Histochemistry and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/34331103","citation_count":9,"is_preprint":false},{"pmid":"31186352","id":"PMC_31186352","title":"The nuclear pore proteins Nup88/214 and T-cell acute lymphatic leukemia-associated NUP214 fusion proteins regulate Notch signaling.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31186352","citation_count":8,"is_preprint":false},{"pmid":"15300515","id":"PMC_15300515","title":"Developing chick embryos express a protein which shares homology with the nuclear pore complex protein Nup88 present in human tumors.","date":"2004","source":"The International journal of developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/15300515","citation_count":8,"is_preprint":false},{"pmid":"27636375","id":"PMC_27636375","title":"Multiple biological processes may be associated with tumorigenesis under NUP88-overexpressed condition.","date":"2016","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/27636375","citation_count":7,"is_preprint":false},{"pmid":"21896994","id":"PMC_21896994","title":"Nup88 mRNA overexpression in colorectal cancers and relationship with p53.","date":"2010","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/21896994","citation_count":6,"is_preprint":false},{"pmid":"18175937","id":"PMC_18175937","title":"Deguelin represses both the expression of nucleophosmin and some nucleoporins: Nup88 and Nup214 in Jurkat cells.","date":"2008","source":"Biological & pharmaceutical bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/18175937","citation_count":6,"is_preprint":false},{"pmid":"17828493","id":"PMC_17828493","title":"Effects of gambogic acid on the regulation of nucleoporin Nup88 in U937 cells.","date":"2007","source":"Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban","url":"https://pubmed.ncbi.nlm.nih.gov/17828493","citation_count":5,"is_preprint":false},{"pmid":"19062711","id":"PMC_19062711","title":"[Effects of gambogic acid on the regulation of nucleoporin Nup88 in HL-60 cells].","date":"2008","source":"Zhonghua zhong liu za zhi [Chinese journal of oncology]","url":"https://pubmed.ncbi.nlm.nih.gov/19062711","citation_count":4,"is_preprint":false},{"pmid":"26839161","id":"PMC_26839161","title":"Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study.","date":"2016","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/26839161","citation_count":3,"is_preprint":false},{"pmid":"17650673","id":"PMC_17650673","title":"[Deguelin regulates cell cycle and nuclear pore complex protein Nup98 and Nup88 in U937 cells in vitro].","date":"2007","source":"Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi","url":"https://pubmed.ncbi.nlm.nih.gov/17650673","citation_count":3,"is_preprint":false},{"pmid":"26762046","id":"PMC_26762046","title":"[Interaction of Flightless I with Nup88 and Importin β].","date":"2015","source":"Sheng wu gong cheng xue bao = Chinese journal of biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/26762046","citation_count":1,"is_preprint":false},{"pmid":"28387602","id":"PMC_28387602","title":"Nucleoporin NUP88/MOS7 is required for manifestation of phenotypes associated with the Arabidopsis CHITIN ELICITOR RECEPTOR KINASE1 mutant cerk1-4.","date":"2017","source":"Plant signaling & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/28387602","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16139,"output_tokens":3199,"usd":0.048201},"stage2":{"model":"claude-opus-4-6","input_tokens":6551,"output_tokens":2570,"usd":0.145508},"total_usd":0.193709,"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\": 1997,\n      \"finding\": \"Nup88 is a novel nuclear pore complex (NPC) component that localizes to the NPC in a CAN/Nup214-dependent manner; depletion of CAN from the NPC results in concomitant loss of Nup88, establishing that Nup88 NPC localization depends on its interaction with CAN/Nup214. Human CRM1 was identified as part of a dynamic subcomplex with CAN/Nup214 and Nup88.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, CAN depletion experiments, overexpression of FG-repeat domain of CAN in cells\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction and depletion experiments with clear functional consequence, foundational paper with 410 citations\",\n      \"pmids\": [\"9049309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nup88 localizes midway between Nup358 and Nup214 on the cytoplasmic face of the NPC and physically interacts with both. RNAi of Nup88 or Nup214 strongly reduces Nup358 at the nuclear envelope, demonstrating that Nup88 and Nup214 together mediate attachment of Nup358 to the NPC. Nup88 and Nup214 show mutual interdependence at the NPC and are not affected by absence of Nup358.\",\n      \"method\": \"RNA interference, immunofluorescence, co-immunoprecipitation, electron microscopy\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal RNAi with clear localization phenotype and Co-IP interaction data, multiple orthogonal methods\",\n      \"pmids\": [\"14993277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The Nup214-Nup88 subcomplex is specifically required for CRM1-mediated nuclear export of the 60S preribosomal subunit via the adaptor NMD3. RNAi depletion of Nup214-Nup88 caused dramatic defects in 60S preribsosome export but only minor defects in other CRM1 cargoes. The coiled-coil region of Nup214 (coinciding with Nup88 recruitment to the NPC) is sufficient for 60S nuclear export, while the FG-repeat domain is dispensable for this function.\",\n      \"method\": \"RNA interference, nuclear export assays, Nup214 domain deletion constructs, fluorescence microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — RNAi with specific export assay readout and domain rescue experiments, multiple orthogonal approaches\",\n      \"pmids\": [\"16675447\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Nup88 directly binds lamin A in vitro and in vivo. The interaction is mediated by the N-terminus of Nup88, which specifically binds the tail domain of lamin A but not lamins B1 or B2. Laminopathy-associated lamin A mutants disrupt the interaction with Nup88 in vitro. Immunoelectron microscopy revealed that Nup88 localizes to both the cytoplasmic and nuclear face of the NPC, suggesting a pool of nuclear-face Nup88 provides a binding site for lamin A.\",\n      \"method\": \"In vitro binding assays, co-immunoprecipitation, immunofluorescence (epitope masking assay), immunoelectron microscopy in Xenopus oocytes, domain mapping\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro reconstitution plus in vivo Co-IP and structural localization, multiple orthogonal methods\",\n      \"pmids\": [\"21289091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NUP88 overexpression sequesters NUP98-RAE1 away from APC/C-CDH1, thereby triggering premitotic proteolysis of PLK1 (polo-like kinase 1). Loss of PLK1 disrupts centrosome separation, causes mitotic spindle asymmetry, merotelic microtubule-kinetochore attachments, lagging chromosomes, and aneuploidy. NUP88 thus functions in a NUP88-NUP98-RAE1-APC/C-CDH1 axis that regulates mitotic entry.\",\n      \"method\": \"Transgenic mouse overexpression, co-immunoprecipitation, Western blotting, live-cell imaging, chromosomal instability assays, PLK1 insufficiency rescue experiments\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vivo mouse model plus Co-IP and rescue experiments, multiple orthogonal methods with strong mechanistic follow-up\",\n      \"pmids\": [\"26731471\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Nup88 is upregulated by hypertonic stress in kidney (IMCD3) cells and acts to retain the transcription factor TonEBP in the nucleus. Silencing Nup88 under hypertonic conditions reduces nuclear retention of TonEBP, blunts transcription of osmoprotective target genes, and reduces cell viability. Under isotonic conditions, nuclear export of TonEBP involves CRM1, but under hypertonic stress the export is CRM1-independent.\",\n      \"method\": \"Antibody microarray, Western blot, qPCR, siRNA knockdown, GFP-TonEBP nuclear retention assay, CRM1 inhibitor (leptomycin B) treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined transcriptional phenotype; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"18606815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"NUP88 depletion in human and mouse cell lines and fetal muscle tissue affects rapsyn, a key regulator of the muscle nicotinic acetylcholine receptor at the neuromuscular junction. Genetic disruption of nup88 in zebrafish causes locomotor defects and neuromuscular junction defects, rescued by wild-type but not disease-mutant Nup88.\",\n      \"method\": \"siRNA knockdown in human/mouse cell lines, zebrafish nup88 morpholino/mutant analysis, immunohistochemistry, rescue experiments with wild-type vs. mutant Nup88\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function in multiple systems (cell lines and zebrafish) with rescue, but rapsyn link established mainly by immunostaining/Western blot rather than direct interaction assay\",\n      \"pmids\": [\"30543681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Nup88 and its partner Nup214 negatively regulate Notch signaling. Loss of Nup88/Nup214 inhibits nuclear export of RBP-J (the DNA-binding component of the Notch pathway), causing increased RBP-J binding to cognate promoter regions and elevated downstream Notch signaling. This was demonstrated in mammalian cells and validated in zebrafish.\",\n      \"method\": \"Reporter gene assays, RNAi knockdown, immunocytochemistry, ChIP-qPCR, zebrafish in vivo validation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (reporter, ChIP, ICC) plus in vivo zebrafish validation; single lab\",\n      \"pmids\": [\"31186352\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Nup88 interacts with Nup62 in a glycosylation-independent and cell-cycle-independent manner, and this interaction stabilizes overexpressed Nup88 by inhibiting proteasome-mediated degradation. Stabilized Nup88 interacts with NF-κB (p65) and sequesters p65 partly into the nucleus of unstimulated cells, inducing NF-κB target genes (Akt, c-Myc, IL-6, BIRC3).\",\n      \"method\": \"Co-immunoprecipitation, proteasome inhibitor assays, Western blotting, immunofluorescence, gene expression analysis\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP with functional follow-up; single lab with moderate mechanistic depth\",\n      \"pmids\": [\"36845732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Overexpression of Nup88 in HeLa cells promotes cell migration and invasion through upregulation of matrix metalloproteinase-12 (MMP-12) at both mRNA and protein levels. Knockdown of Nup88 suppresses migration and invasion, and pharmacological inhibition of MMP-12 enzymatic activity suppresses Nup88-overexpression-induced invasion.\",\n      \"method\": \"Overexpression and RNAi knockdown, migration/invasion assays, RT-PCR, Western blot, MMP-12 inhibitor treatment\",\n      \"journal\": \"Histochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — loss- and gain-of-function with defined molecular output (MMP-12) and pharmacological rescue; single lab\",\n      \"pmids\": [\"34331103\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NUP88 overexpression blocks MISP (mitotic interactor and substrate of PLK1) phosphorylation, which is required for normal spindle formation and accurate chromosome segregation during mitosis. NUP88 was found to interact with MISP by proteomic/interactome analysis.\",\n      \"method\": \"Subcellular proteomic pulldown/interactome analysis, phosphorylation assays\",\n      \"journal\": \"Genes, chromosomes & cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single pulldown/proteomic identification with limited mechanistic follow-up; single lab\",\n      \"pmids\": [\"27636375\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Flightless I (FLII) interacts with Nup88 via its LRR domain, as demonstrated by GST pulldown and co-immunoprecipitation, suggesting FLII may participate in nuclear export through interaction with Nup88.\",\n      \"method\": \"GST pulldown, co-immunoprecipitation, domain deletion constructs\",\n      \"journal\": \"Sheng wu gong cheng xue bao = Chinese journal of biotechnology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single pulldown and Co-IP; no further functional validation of the interaction's consequence\",\n      \"pmids\": [\"26762046\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP88 is a cytoplasmic-face nuclear pore complex component that depends on CAN/NUP214 for its NPC localization, physically scaffolds NUP358 and lamin A at the NPC, participates with NUP214 in CRM1-mediated 60S preribosomal export, regulates nuclear retention of transcription factors (NF-κB, TonEBP, RBP-J) by modulating their nuclear export, and when overexpressed sequesters the NUP98-RAE1 complex away from APC/C-CDH1 to trigger premitotic PLK1 degradation, thereby promoting chromosomal instability and aneuploidy.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP88 is a cytoplasmic-face nuclear pore complex (NPC) component that scaffolds NPC architecture, regulates selective nuclear export, and controls mitotic fidelity. Its NPC localization depends on CAN/NUP214, and together these nucleoporins mediate attachment of NUP358 to the pore and are specifically required for CRM1-dependent export of 60S preribosomal subunits [PMID:9049309, PMID:14993277, PMID:16675447]. NUP88 directly binds lamin A via its N-terminus and modulates nuclear retention of transcription factors including NF-κB, TonEBP, and RBP-J, thereby influencing Notch signaling and osmotic stress responses [PMID:21289091, PMID:18606815, PMID:31186352, PMID:36845732]. When overexpressed—a frequent event in tumors—NUP88 sequesters the NUP98–RAE1 complex away from APC/C-CDH1, causing premitotic PLK1 degradation, defective centrosome separation, and chromosomal instability [PMID:26731471].\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Identifying NUP88 as an NPC component whose pore localization depends on CAN/NUP214 established the first molecular dependency in the cytoplasmic nucleoporin network and linked NUP88 to the CRM1 export machinery.\",\n      \"evidence\": \"Co-immunoprecipitation and CAN depletion experiments in human cells\",\n      \"pmids\": [\"9049309\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the NUP88–NUP214–CRM1 subcomplex unknown\", \"Whether NUP88 contacts CRM1 directly or only via NUP214 unresolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrating that NUP88 and NUP214 are both required for NUP358 attachment to the NPC revealed NUP88 as a structural scaffold of the cytoplasmic filament network, resolving how the outermost pore components are anchored.\",\n      \"evidence\": \"RNAi of NUP88/NUP214 with immunofluorescence and electron microscopy readouts\",\n      \"pmids\": [\"14993277\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding interface between NUP88 and NUP358 not mapped\", \"Whether NUP88 loss affects NPC transport beyond NUP358-dependent pathways unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Showing that the NUP214–NUP88 subcomplex is specifically required for CRM1-mediated 60S preribosomal export—but largely dispensable for other CRM1 cargoes—revealed cargo selectivity at individual NPC subcomplexes.\",\n      \"evidence\": \"RNAi depletion coupled with specific nuclear export assays and NUP214 domain rescue constructs\",\n      \"pmids\": [\"16675447\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How NUP88 itself contributes to 60S selectivity versus serving only as a NUP214 anchor unresolved\", \"Other potential cargo-specific export roles of NUP88 not surveyed\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Finding that NUP88 upregulation under hypertonic stress retains TonEBP in the nucleus provided the first evidence that NUP88 levels modulate transcription factor localization in a physiological signaling context.\",\n      \"evidence\": \"siRNA knockdown in kidney IMCD3 cells with GFP-TonEBP nuclear retention assays and CRM1 inhibitor treatment\",\n      \"pmids\": [\"18606815\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which NUP88 retains TonEBP independently of CRM1 not defined\", \"Whether NUP88 directly contacts TonEBP or acts indirectly unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrating direct NUP88–lamin A binding and showing disruption by laminopathy mutations expanded NUP88 function beyond the cytoplasmic face to a structural link between the NPC and the nuclear lamina.\",\n      \"evidence\": \"In vitro binding assays, co-immunoprecipitation, immunoelectron microscopy in Xenopus oocytes\",\n      \"pmids\": [\"21289091\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of NUP88–lamin A disruption on NPC integrity or transport not established\", \"Whether loss of this interaction contributes to laminopathy phenotypes untested in vivo\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Elucidating the NUP88→NUP98-RAE1→APC/C-CDH1→PLK1 axis explained how NUP88 overexpression causes chromosomal instability, providing a mechanistic link between nucleoporin dysregulation and aneuploidy in cancer.\",\n      \"evidence\": \"Transgenic NUP88-overexpressing mice, co-immunoprecipitation, live-cell imaging, PLK1 rescue experiments\",\n      \"pmids\": [\"26731471\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether endogenous NUP88 levels regulate PLK1 during normal mitosis unknown\", \"Tissue-specific thresholds for NUP88 overexpression to induce CIN not determined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linking NUP88 loss of function to neuromuscular junction defects via rapsyn dysregulation in zebrafish and mammalian cells expanded the gene's physiological roles to tissue-specific developmental processes.\",\n      \"evidence\": \"siRNA in human/mouse cells, zebrafish mutant analysis with wild-type vs. mutant rescue\",\n      \"pmids\": [\"30543681\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NUP88 directly interacts with rapsyn or acts via nuclear transport of an upstream regulator unresolved\", \"Specific NUP88 mutations found in patients not functionally characterized at the NPC level\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that NUP88/NUP214 loss inhibits nuclear export of RBP-J, thereby amplifying Notch signaling, revealed NUP88 as a negative regulator of a major developmental signaling pathway.\",\n      \"evidence\": \"Reporter assays, ChIP-qPCR, RNAi in mammalian cells, zebrafish validation\",\n      \"pmids\": [\"31186352\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether RBP-J export is CRM1-dependent through NUP88 or uses an alternative pathway not resolved\", \"Physiological contexts where NUP88-mediated Notch regulation is rate-limiting unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying NUP62 as a stabilizer of overexpressed NUP88 (by blocking proteasomal degradation) and showing that stabilized NUP88 sequesters NF-κB p65 in the nucleus clarified how NUP88 overexpression in tumors could constitutively activate NF-κB target genes.\",\n      \"evidence\": \"Co-immunoprecipitation, proteasome inhibitor assays, gene expression analysis in human cells\",\n      \"pmids\": [\"36845732\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NUP88–p65 interaction is direct not determined\", \"In vivo relevance of NUP62-dependent NUP88 stabilization in tumors not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural model of how NUP88 simultaneously scaffolds NUP214, NUP358, and lamin A at the NPC, and how its stoichiometric balance controls the switch between transport and mitotic regulation, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No high-resolution structure of NUP88 in the context of the intact NPC subcomplex\", \"Mechanism by which NUP88 selectively modulates export of specific transcription factors versus bulk CRM1 cargo unknown\", \"Whether NUP88 overexpression-driven CIN and NF-κB activation operate through independent or convergent oncogenic pathways not determined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 5, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 10]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 8]}\n    ],\n    \"complexes\": [\n      \"NUP88-NUP214 subcomplex\",\n      \"Nuclear pore complex (NPC)\"\n    ],\n    \"partners\": [\n      \"NUP214\",\n      \"NUP358\",\n      \"LMNA\",\n      \"NUP98\",\n      \"RAE1\",\n      \"NUP62\",\n      \"CRM1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}