Affinage

NUP98

Nuclear pore complex protein Nup98-Nup96 · UniProt P52948

Length
1817 aa
Mass
197.6 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP98 is a bifunctional FG/GLFG-repeat nucleoporin that supports nucleocytoplasmic transport at the nuclear pore complex (NPC) while also acting in the nuclear interior to regulate gene expression (PMID:9015297, PMID:11950939). NUP98 is co-translated with NUP96 as a 186-kDa precursor whose autoproteolytic cleavage is required to target both products to the nucleoplasmic face of the NPC and to nucleate a conserved NUP96-NUP107-Sec13 subcomplex (PMID:10087256, PMID:14517296); the same cleavage-dependent C-terminal site mediates binding to both the cytoplasmic nucleoporin Nup88 and to Nup96, and loss of NUP98 impairs assembly of cytoplasmic-face nucleoporins and receptor-mediated import of selective cargoes (PMID:12589057, PMID:11248054). At the pore, NUP98 enables export of multiple RNA classes (PMID:9015297), serving as a docking platform whose GLFG domain assembles a ternary mRNA-export complex with Rae1/Gle2 and TAP (PMID:12637516) and acting as a RanGTP-dependent cofactor for Crm1-mediated protein export through its N-terminal FG repeats (PMID:20375145). The Rae1·NUP98 module forms a seven-bladed β-propeller heterocomplex with single-stranded RNA-binding capacity (PMID:20498086), and beyond transport this complex governs mitotic fidelity by inhibiting APC-Cdh1-mediated securin ubiquitination, preventing premature sister-chromatid separation and aneuploidy (PMID:16355229). A mobile intranuclear pool of NUP98, dependent on ongoing transcription, associates with developmentally regulated genes and active promoters (PMID:11950939, PMID:23468646), where it recruits the Wdr82-Set1A/COMPASS complex to deposit H3K4me3 at transcription start sites (PMID:29269482), stimulates the ATPase activity of the DHX9 helicase at shared gene loci (PMID:28221134), and post-transcriptionally protects specific mRNAs such as p21 from exosomal degradation (PMID:23102701). In leukemia, NUP98 fusion oncoproteins exploit the intrinsically disordered FG repeats to drive liquid-liquid phase separation into nuclear condensates that partition transcriptional coactivators—CBP/p300, MLL1/KMT2, the NSL complex, BRD4, and MYST acetyltransferases KAT6A/KAT7—and are targeted to developmental loci through partner chromatin-reader domains (e.g. the PHF23 PHD finger binding H3K4me3) and through prebound Crm1, sustaining aberrant HOX/MEIS1 and CDK6 transcriptional programs that drive transformation (PMID:9858599, PMID:17589499, PMID:27889185, PMID:26740045, PMID:34903620, PMID:32344427, PMID:39922194, PMID:40536430, PMID:32620764, PMID:24535671). The Nup98-Rae1 complex is additionally hijacked by viral antagonists, including SARS-CoV-2 ORF6 and VSV matrix protein, to block host transport and immune gene induction (PMID:33097660, PMID:24927547).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    Established NUP98 as a functional requirement for RNA export rather than protein import, defining its core role at the pore.

    Evidence Anti-Nup98 antibody injection into Xenopus oocyte nuclei with class-specific RNA export and import assays

    PMID:9015297

    Open questions at the time
    • Did not identify the molecular export factors NUP98 docks
    • tRNA export and protein import unaffected, leaving pathway selectivity unexplained
  2. 1999 High

    Resolved the biogenesis of NUP98 and NUP96 from a single precursor, showing autoproteolytic cleavage is required for correct NPC targeting and subcomplex assembly.

    Evidence Biochemical fractionation, mutagenesis, immunoEM, and in vitro autocleavage assays in rat liver nuclei

    PMID:10087256

    Open questions at the time
    • Did not address the intranuclear transport-independent functions of NUP98
    • in vivo consequence of cleavage failure not tested
  3. 1999 High

    Identified the FG repeats as a transactivation domain in the NUP98-HOXA9 oncofusion, linking a transport motif to coactivator recruitment in transformation.

    Evidence NIH 3T3 transformation, luciferase transactivation, and co-IP with CBP/p300

    PMID:9858599

    Open questions at the time
    • Did not establish chromatin targeting of the fusion
    • physiological vs oncogenic FG-repeat function not yet distinguished
  4. 2001 High

    Genetic disruption in mice demonstrated NUP98 is required for cytoplasmic-face nucleoporin assembly and selective cargo import, separating its roles from NUP96.

    Evidence Murine NUP98 gene targeting with immunofluorescence and selective cargo import assays

    PMID:11248054

    Open questions at the time
    • Mechanism of cytoplasmic nucleoporin recruitment by NUP98 not resolved here
  5. 2003 Medium

    Mapped the GLFG-domain binding sites for the mRNA export machinery and the cleavage-dependent dual binding of NUP98 to Nup88 and Nup96.

    Evidence In vitro pulldown/competition binding and domain mapping; immunoEM and mutagenesis

    PMID:12589057 PMID:12637516

    Open questions at the time
    • TAP-Rae1 binding overlap defined in vitro without in vivo export consequence
    • single-lab binding data
  6. 2005 High

    Defined a transport-independent mitotic function: the Rae1-NUP98 complex inhibits APC-Cdh1 to safeguard chromosome segregation.

    Evidence Mouse haploinsufficiency genetics, APC-Cdh1 co-IP, in vitro securin ubiquitination, and aneuploidy flow cytometry

    PMID:16355229

    Open questions at the time
    • Structural basis of APC-Cdh1 inhibition not defined
    • how the same complex switches between transport and mitotic roles unknown
  7. 2010 High

    Provided atomic-resolution structure of the Rae1·NUP98 GLEBS complex and revealed its single-stranded RNA-binding activity, and separately defined NUP98 as a RanGTP-dependent Crm1 export cofactor.

    Evidence 1.65 Å crystal structure with mutagenesis and RNA-binding assays; RanGTP-dependent co-IP, FG-repeat mutagenesis, and antibody export inhibition

    PMID:20375145 PMID:20498086

    Open questions at the time
    • Functional RNA target of the Rae1·NUP98 RNA-binding surface not identified
    • RanBP3 modulation mechanism not detailed
  8. 2013 High

    Showed NUP98 binds developmental genes at both the pore and the nuclear interior and post-transcriptionally protects specific mRNAs, broadening its role to direct gene regulation.

    Evidence Genome-wide ChIP-seq in human ESCs with dominant-negative fragment; single-molecule mRNA analysis and exosome degradation assays for p21

    PMID:23102701 PMID:23468646

    Open questions at the time
    • Mechanism distinguishing pore-tethered vs interior gene regulation incomplete
    • exosome-protection mechanism for mRNAs beyond p21/14-3-3σ not generalized
  9. 2016 High

    Established that NUP98 fusions are recruited to HOX loci via prebound Crm1 and physically engage MLL1/NSL complexes for aberrant transcription.

    Evidence Genome-wide ChIP-seq, leptomycin B Crm1 inhibition, and reciprocal co-IP of multiple fusions with MLL1/NSL

    PMID:26740045 PMID:27889185

    Open questions at the time
    • Whether Crm1 recruits wild-type NUP98 to the same loci unresolved
    • biophysical nature of the chromatin 'dots' not yet defined
  10. 2017 High

    Defined the wild-type chromatin function of NUP98: recruitment of Wdr82-Set1A/COMPASS for H3K4me3 deposition and stimulation of the DHX9 helicase, and showed fusions mislocalize H3K4me3.

    Evidence ChIP-seq with Nup98/Wdr82 depletion and Set1A/H3K4me3 ChIP; in vitro ATPase stimulation and RNA-facilitated binding assays

    PMID:28221134 PMID:29269482

    Open questions at the time
    • How transcription-dependent NUP98 mobility couples to COMPASS recruitment unclear
    • DHX9 substrate transcripts in vivo not enumerated
  11. 2022 High

    Showed FG-repeat-driven liquid-liquid phase separation is the organizing principle of NUP98-fusion oncogenesis, concentrating chromatin regulators including SMARCA5.

    Evidence In vitro LLPS reconstitution, FG-repeat mutagenesis, AP-MS, FRAP, and hematopoietic transformation assays

    PMID:34903620 PMID:35073946

    Open questions at the time
    • Whether wild-type NUP98 phase behavior contributes to normal gene regulation untested
    • condensate composition rules across diverse fusions incomplete
  12. 2025 High

    Dissected the division of labor between fusion partner reader domains (targeting) and FG repeats (composition/activation), revealing a feedforward read-and-write loop and actionable MYST-HAT dependencies.

    Evidence In vitro condensate reconstitution, mutagenesis, condensate proteomics, ChIP-seq, and genetic/pharmacological KAT6A/7 loss-of-function with xenografts

    PMID:39922194 PMID:40536430

    Open questions at the time
    • Generalizability of the read-write loop across all NUP98 fusion classes not fully mapped
    • therapeutic window of HAT and PHD inhibition not established here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NUP98's transport, mitotic, and chromatin-regulatory activities are integrated and switched in normal cells, and whether condensate-based regulation operates at endogenous NUP98, remains unresolved.
  • No unified model linking pore residence, intranuclear mobility, and gene activation
  • endogenous NUP98 phase behavior in normal hematopoiesis uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005635 nuclear envelope 3 GO:0000228 nuclear chromosome 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2
Partners
CRM1DHX9NUP88NUP96RAE1SEC13TAPTPR
Complex memberships
NUP96-NUP107-Sec13 NPC subcomplexNUP98-Rae1-TAP mRNA export complexRae1-NUP98 complexWdr82-Set1A/COMPASS complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NUP98 and NUP96 are both generated by autoproteolytic cleavage of a 186-kDa precursor protein; proteolytic cleavage is required for correct targeting of both NUP98 and NUP96 to the nucleoplasmic side of the NPC, and a complex containing NUP96, NUP107, and Sec13-related proteins was identified as a conserved NPC subcomplex. Biochemical fractionation of rat liver nuclei, mutational analysis, immunoelectron microscopy, in vitro autoproteolytic cleavage assays The Journal of cell biology High 10087256
1997 Nuclear injection of anti-Nup98 antibodies in Xenopus oocytes inhibits export of snRNAs, 5S RNA, large ribosomal RNAs, and mRNA, but not tRNA, and does not affect import of karyophilic proteins or snRNPs, establishing Nup98 as an essential component of multiple RNA export pathways but not protein import. Antibody injection into Xenopus laevis oocyte nucleus with functional RNA export assays The Journal of cell biology High 9015297
2002 Nup98 is found both at the nuclear pore complex and within the nucleus at a novel intranuclear structure termed the GLFG body; the GLFG domain of Nup98 is required for targeting to this structure; Nup98 is mobile and moves between these localizations; this mobility is dependent on ongoing transcription by RNA polymerases I and II. GFP-Nup98 live-cell imaging, FRAP (photobleaching), transcription inhibitor treatments, domain deletion analysis Molecular biology of the cell High 11950939
2003 Nup98 is localized on both the nuclear and cytoplasmic faces of the nuclear pore; the pore-targeting domain of Nup98 directly interacts with the cytoplasmic nucleoporin Nup88; the same site within Nup98 binds both Nup88 (cytoplasmic face) and Nup96 (nuclear face); autoproteolytic cleavage of the Nup98 C-terminus is required for both binding interactions. Immunofluorescence, immunoelectron microscopy, direct binding assays, point mutation blocking cleavage Molecular biology of the cell High 12589057
2001 Disruption of murine NUP98 (leaving NUP96 intact) causes inefficient assembly of cytoplasmic-face nucleoporins (NUP358, NUP214, NUP88, p62) into nuclear pores, with these nucleoporins instead associating with annulate lamellae; NUP98-deficient cells show impaired transport receptor-mediated docking and nuclear import of NLS and M9 signal-containing substrates, but not ribosomal protein L23a or U1A import. Gene targeting in mice, immunofluorescence, nuclear pore import assays with selective cargo classes Proceedings of the National Academy of Sciences of the United States of America High 11248054
2005 Rae1 and Nup98 form a complex with Cdh1-activated APC (APC-Cdh1) in early mitosis and specifically inhibit APC-Cdh1-mediated ubiquitination of securin; combined Rae1 and Nup98 haploinsufficiency in mice causes premature securin degradation, sister chromatid separation, and severe aneuploidy. Mouse haploinsufficiency genetics, co-immunoprecipitation of APC-Cdh1 complex, in vitro ubiquitination assay, flow cytometry for aneuploidy Nature High 16355229
1999 The NUP98-HOXA9 fusion protein's FG repeats act as potent transcriptional transactivation domains that physically and functionally interact with transcriptional coactivators CBP and p300; this FG-repeat-mediated transactivation is essential for transformation of NIH 3T3 cells. NIH 3T3 transformation assay, luciferase reporter transactivation assay, co-immunoprecipitation with CBP/p300, domain deletion/mutation analysis Molecular and cellular biology High 9858599
2003 Nup98, Rae1/Gle2, and TAP form a ternary mRNA export complex; TAP binds with highest affinity to a specific region within the GLFG domain of Nup98 (not all FG repeats equally); Gle2/Rae1 binds Nup98 and TAP at adjacent but overlapping sites, and when Gle2 is bound to Nup98 it can no longer directly interact with TAP. In vitro binding assays (pulldown), domain mapping, competition binding experiments The Journal of biological chemistry Medium 12637516
2010 Crystal structure of human Rae1 in complex with the GLEBS motif of Nup98 at 1.65 Å resolution shows Rae1 forms a seven-bladed β-propeller; the C-terminal arm of the Nup98 GLEBS hairpin binds an invariant hydrophobic surface on the top face of Rae1; a tandem glutamate element in the C-terminal arm is critical for complex formation; the Rae1·Nup98 complex possesses single-stranded RNA-binding capability. X-ray crystallography (1.65 Å), mutagenesis, RNA-binding assays Proceedings of the National Academy of Sciences of the United States of America High 20498086
1999 Nup98 participates in HIV-1 Rev-hCRM1-mediated nuclear export; Rev recruits Nup98 and Nup214 to the nucleolus; FG-repeat domains of Nup98 and Nup214 competitively inhibit Rev/RRE-mediated expression; upon actinomycin D treatment Nup98 (but not Nup214 or Nup153) translocates to the cytoplasm, demonstrating it can act as a soluble factor. Nucleolar recruitment assays, competitive inhibition reporter assays, immunofluorescence after actinomycin D treatment Journal of virology Medium 9847314
2001 Nup98 associates with the intranuclear filamentous protein network of TPR; in vitro translated TPR binds in vitro translated Nup98, and via Nup98 also associates with Nup96; immunofluorescence shows colocalization of Nup98 and TPR including at perinucleolar sites. In vitro translation/binding assay, double-immunofluorescence microscopy, immunoelectron microscopy Proceedings of the National Academy of Sciences of the United States of America Medium 11248057
2003 Sec13 stably interacts with Nup96 at the nuclear pore complex via its WD repeat region binding to the N-terminal region of Nup96; Sec13 shuttles between intranuclear sites and the cytoplasm; cotransfection of the Sec13-binding domain of Nup96 decreased the mobile pool of Sec13, confirming the interaction in vivo. Yeast two-hybrid, biochemical assays, immunofluorescence, confocal and immunoelectron microscopy, FRAP, in vivo competition cotransfection Molecular and cellular biology High 14517296
2010 Nup98 functions as a cofactor for Crm1-mediated nuclear protein export; Nup98 physically and functionally interacts with Crm1 in a RanGTP-dependent manner through its N-terminal FG repeat region; this activity is modulated by RanBP3; cytoplasmic microinjection of anti-Nup98 antibody inhibits Crm1-dependent nuclear export. Leptomycin B treatment, co-immunoprecipitation (RanGTP-dependent), mutational analysis, microinjection of anti-Nup98 antibodies with nuclear export assay Molecular biology of the cell High 20375145
2007 NUP98-NSD1 fusion protein binds genomic elements adjacent to HoxA7 and HoxA9, maintains H3K36 methylation and histone acetylation at these loci, and prevents EZH2-mediated transcriptional repression of the Hox-A locus; deletion of the NUP98 FG-repeat domain or inactivating mutations in the NSD1 H3K36 methyltransferase activity abrogated both Hox-A gene activation and myeloid progenitor immortalization. Chromatin immunoprecipitation (ChIP), mutagenesis of catalytic site and FG domain, in vitro immortalization assay, in vivo AML mouse model Nature cell biology High 17589499
2016 NUP98 fusion proteins (NUP98-HOXA9, NUP98-HOXD13, NUP98-NSD1, NUP98-PHF23, NUP98-TOP1) physically interact with the MLL1 and NSL histone-modifying complexes; NUP98-HOXA9 and MLL1 co-occupy Hox gene promoter regions on chromatin; MLL1 is required for proliferation of NUP98-HOXA9 cells and for NUP98-HOXA9-induced gene expression. Co-immunoprecipitation, ChIP-sequencing, MLL1 genetic inactivation with proliferation and gene expression readouts Cancer cell High 27889185
2013 NUP98 associates with developmentally regulated genes in human embryonic stem cells at both the nuclear periphery (pore-embedded) and the nuclear interior (away from pores); overexpression of a dominant-negative NUP98 fragment decreases expression of NUP98-bound genes; two spatial modes of gene regulation are distinguished by gene activation state. Genome-wide ChIP-seq in human ESCs, dominant-negative NUP98 fragment overexpression with gene expression analysis PLoS genetics Medium 23468646
2017 In hematopoietic cells, Nup98 binds predominantly to transcription start sites and recruits the Wdr82-Set1A/COMPASS complex, which is required for H3K4me3 deposition; depletion of Nup98 or Wdr82 abolishes Set1A recruitment to chromatin and ablates H3K4me3 at adjacent promoters; expression of a leukemogenic NUP98 fusion protein causes mislocalization of H3K4me3 and up-regulation of associated genes. ChIP-seq, siRNA knockdown of Nup98 and Wdr82 with H3K4me3 and Set1A ChIP, co-immunoprecipitation Genes & development High 29269482
2012 Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome; Nup98 is similarly required for expression of the p53 target 14-3-3σ; this function is distinct from NUP98 fusion oncoproteins' activities. Single-molecule mRNA analysis, conventional mRNA analysis, 3'UTR-Nup98 complex identification, siRNA knockdown, exosome activity assays Molecular cell High 23102701
2020 SARS-CoV-2 Orf6 localizes to the nuclear pore complex and directly interacts with the Nup98-Rae1 complex via its C-terminal domain to impair docking of karyopherin/importin cargo complexes, blocking STAT1 and STAT2 nuclear translocation and suppressing interferon-stimulated gene induction; a Met58-to-Arg substitution in Orf6 abolishes binding to Nup98-Rae1 and eliminates its IFN antagonistic function. Co-immunoprecipitation, nuclear import assays for STAT1/STAT2, immunofluorescence, site-directed mutagenesis (M58R) Proceedings of the National Academy of Sciences of the United States of America High 33097660
2021 SARS-CoV-2 ORF6 blocks both nuclear import and mRNA nuclear export through interactions with Rae1 and Nup98 that map to the C-terminus of ORF6 (Met58); overexpression of Rae1 restores reporter gene expression in presence of ORF6; SARS-CoV-2 ORF6 more strongly co-purifies with Rae1 and Nup98 than SARS-CoV ORF6. Co-purification assays, reporter expression assays, nuclear poly(A) RNA accumulation assays, Rae1 overexpression rescue, M58 mutagenesis mBio High 33849972
2014 Crystal structure at 3.15 Å of the VSV matrix protein M in complex with Rae1·Nup98 reveals M contacts the Rae1 β-propeller via a 'finger' (containing Met51) and 'thumb'; M protein occupies the nucleic acid-binding site of Rae1·Nup98 and competitively inhibits oligonucleotide binding to this complex; the finger peptide alone is sufficient to compete for nucleic acid binding. X-ray crystallography (3.15 Å), in vitro competition binding assay with oligonucleotides, synthetic peptide competition Proceedings of the National Academy of Sciences of the United States of America High 24927547
2012 VSV M protein preferentially interacts with intermediate-molecular-weight Rae1-Nup98 complexes; silencing Rae1 reduces VSV's ability to inhibit host transcription but not nuclear mRNA accumulation or translation inhibition; M protein-Rae1-Nup98 complexes are associated with the chromatin fraction, consistent with a role in transcription inhibition. Size exclusion chromatography, sedimentation velocity analysis, siRNA knockdown, chromatin fractionation, transcription/translation reporter assays in VSV-infected cells PLoS pathogens Medium 23028327
2017 The DExH/D-box helicase DHX9 is an intranuclear binding partner of Nup98; the FG/GLFG region of Nup98 binds N- and C-terminal regions of DHX9 in an RNA-facilitated manner; Nup98 binding stimulates the ATPase activity of DHX9; Nup98 and DHX9 bind interdependently to similar gene loci and their transcripts. In vitro binding assays, ATPase activity assay, transcriptional reporter assay, co-occupancy analysis (ChIP/RNA-seq), RNA facilitation experiments eLife High 28221134
2010 Nup98-homeodomain fusion proteins dynamically interact with endogenous Nup98 during interphase, mislocalizing the intranuclear fraction of Nup98 without altering Nup98 levels at the NPC; during mitosis, the fusions localize entirely to kinetochores and chromosome arms (sites of APC/C activity) rather than interacting with endogenous Nup98. Live-cell fluorescence microscopy, cell cycle staging, co-localization with APC/C markers Molecular biology of the cell Medium 20237156
2013 NUP98 fusion oncoproteins (but not wild-type NUP98) cause mitotic spindle defects and chromosome missegregation; NUP98 fusions physically interact with APC/C-Cdc20 and displace the BubR1 SAC component, causing premature securin degradation and spindle assembly checkpoint slippage; wild-type NUP98 stability is controlled by a PEST sequence absent in oncoproteins, whose deletion reproduces the aberrant SAC-interfering activity. Co-immunoprecipitation of APC/C-Cdc20, chromosome segregation assays (live imaging), PEST sequence deletion mutagenesis, securin degradation assay Cancer research Medium 24371226
2011 RAE1 knockdown disrupts proper chromosome segregation and ablates RAE1 but not HDAC1 expression/localization; rescue experiments confirm the RAE1-NUP98 complex orchestrates proper chromosome segregation; in NUP98-HOXA9-transfected cells, RAE1 protein is reduced and mislocalized, consistent with RAE1 contributing to NUP98-fusion-mediated leukemogenesis. siRNA knockdown, rescue experiments, immunofluorescence, chromosome segregation analysis, NUP98-HOXA9 transgenic mouse analysis Cell cycle (Georgetown, Tex.) Medium 21467841
2016 Nup98-HoxA9 is preferentially targeted to Hox cluster regions where Crm1 is prebound on chromatin; leptomycin B (Crm1 inhibitor) disassembles nuclear Nup98-HoxA9 dots, abolishes chromatin binding, and reverses Hox gene activation; Crm1 physically interacts with Nup98-HoxA9 to mediate its targeting to Hox loci. Genome-wide ChIP-seq, leptomycin B treatment, co-immunoprecipitation, immunofluorescence, gene expression analysis eLife High 26740045
2022 NUP98-HOXA9 and related NUP98 fusion oncoproteins form nuclear condensates (liquid-liquid phase separation) via homotypic and heterotypic interactions; the intrinsically disordered FG-repeat region of NUP98 drives LLPS in vitro; condensate formation is required for aberrant transcriptional activity and transformation of hematopoietic stem/progenitor cells. In vitro LLPS assays, mutagenesis of FG repeats, nuclear condensate live imaging, hematopoietic transformation assays, transcriptional reporter assays Cancer discovery High 34903620
2022 NUP98-NSD1 core interactome binding is largely dependent on its FG-repeat domains, which mediate formation of liquid-like phase-separated nuclear condensates; SMARCA5 (ISWI family member) is identified as a condensate constituent that interacts with NUP98-NSD1 and is required for hematopoietic cell transformation; SMARCA5 inhibition impairs transformation without disrupting condensate formation itself. Affinity purification-mass spectrometry (AP-MS), FRAP, b-isoxazole condensate assay, siRNA/pharmacological SMARCA5 inhibition, proximity ligation assay, methylcellulose transformation assay Journal of experimental & clinical cancer research High 35073946
2020 NUP98 fusion proteins directly bind to CDK6 gene loci and are required for CDK6 transcription; CDK6 loss severely attenuates NUP98-fusion-driven leukemogenesis; NUP98-fusion AML is sensitive to pharmacologic CDK6 inhibition in vitro and in vivo. ChIP-seq (chromatin occupancy of NUP98 fusions), inducible fusion protein inactivation with transcriptome profiling, CDK6 genetic loss-of-function, CDK6 inhibitor treatment in mouse and in vivo models Blood High 32344427
2017 The second FG repeat domain of the NUP98 moiety of NUP98-HOXA9 is required for cell immortalization and leukemogenesis; NUP98-HOXA9 interacts with MLL via this FG repeat domain; in the absence of MLL, NUP98-HOXA9 fails to be recruited to the HOXA locus and HOXA gene expression is not induced. Domain deletion mutagenesis, co-immunoprecipitation (NUP98-HOXA9 with MLL), ChIP at HOXA locus, MLL conditional knockout in NUP98-HOXA9 cells Leukemia High 28210005
2022 Nup98's role in transcriptional memory in Drosophila is to stabilize the forward rate of conversion from low to high expressing transcriptional state; this memory establishment is independent of actual transcription during the initial exposure, as inhibiting transcription during initial ecdysone exposure does not prevent memory establishment. Single-molecule RNA FISH (smFISH), mathematical modeling, transcription inhibitor experiments, Drosophila cell system with ecdysone stimulation eLife Medium 35289742
2025 In NUP98-PHF23 fusion, the PHD domain targets condensates to H3K4me3/2-marked developmental genes, while the FG repeats determine condensate composition and gene activation; FG repeats are necessary and sufficient to partition specific transcriptional regulators (KMT2/MLL H3K4 methyltransferases, histone acetyltransferases, BRD4) into condensates; FG-repeat-tethered condensates initiate a feedforward loop of reading-and-writing active histone modifications. Mutagenesis, proteomics (condensate composition analysis), ChIP-seq (genomics), in vitro condensate reconstitution, tethering assay Molecular cell High 39922194
2025 MYST family histone acetyltransferases KAT6A and KAT7 associate with NUP98 fusion oncoproteins on chromatin and within condensates; KAT6A/7 are molecular dependencies in NUP98-rearranged leukemia; KAT6A/7 inhibition decreases H3K23ac, displaces NUP98::HOXA9 from chromatin at the Meis1 locus, and drives myeloid differentiation. Co-immunoprecipitation/ChIP co-occupancy, genetic KAT6A/7 inactivation, pharmacological HAT inhibition, H3K23ac ChIP, xenograft mouse models Cancer discovery High 40536430
2014 NUP98-PHF23 fusion binds H3K4me3-marked chromatin via the PHF23 PHD finger; disulfiram directly inhibits PHD-H3K4me3 binding and kills NUP98-PHF23 AML cells; NMR analysis confirms H3K4me3 binding by PHD fingers of PHF23, KDM5A, and BPTF at conserved sites, suggesting a common PHD-dependent chromatin-targeting mechanism for this class of NUP98 fusions. ChIP demonstrating H3K4me3 co-occupancy, NMR analysis of PHD-H3K4me3 interaction, disulfiram PHD-inhibition cell viability assay Nature communications / Cancer discovery High 24535671 32620764
2013 Nup98 specifically regulates nuclear-to-cytoplasmic transport of galectin-3; Nup98 interacts with galectin-3 at the nuclear membrane and promotes galectin-3 cytoplasmic translocation; silencing Nup98 retains galectin-3 in the nucleus, retards cell growth, and suppresses β-catenin pathway target gene expression (cyclin D1, FRA-1). Co-immunoprecipitation, siRNA knockdown, immunofluorescence, cell growth assays, gene expression analysis Biochemical and biophysical research communications Medium 23541576
2006 Nup96+/− mice with selectively low Nup96 levels display downregulated MHC I and MHC II, ICAM-1, and impaired IFN-alpha and gamma-mediated induction of these proteins, demonstrating Nup96 (the NUP98 precursor cleavage product) is specifically required for proper nuclear transport and expression of interferon-regulated proteins and immune function. Nup96+/- mouse genetics, interferon stimulation assays, MHC expression analysis, T cell functional assays, viral infection susceptibility Immunity High 16546098

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proceedings of the National Academy of Sciences of the United States of America 444 33097660
1996 Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nature genetics 440 8563753
2007 NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nature cell biology 354 17589499
1999 CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity. Molecular and cellular biology 283 9858599
2011 NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights. Blood 275 21948299
2002 Nup98 is a mobile nucleoporin with transcription-dependent dynamics. Molecular biology of the cell 220 11950939
1999 A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. The Journal of cell biology 217 10087256
2005 NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia. Blood 198 15755899
1997 The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways. The Journal of cell biology 191 9015297
2005 The Rae1-Nup98 complex prevents aneuploidy by inhibiting securin degradation. Nature 157 16355229
2022 Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation. Cancer discovery 150 34903620
2003 Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Molecular biology of the cell 150 12589057
2016 NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis. Cancer cell 140 27889185
1999 Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev. Journal of virology 136 9847314
2022 The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML. Blood 132 34582559
2013 Dynamic association of NUP98 with the human genome. PLoS genetics 129 23468646
2021 SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98. mBio 126 33849972
2020 Mechanistic insights and potential therapeutic approaches for NUP98-rearranged hematologic malignancies. Blood 122 32766874
2001 Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function. Proceedings of the National Academy of Sciences of the United States of America 121 11248054
2003 Complex formation among the RNA export proteins Nup98, Rae1/Gle2, and TAP. The Journal of biological chemistry 113 12637516
2006 NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique. Leukemia 108 16467868
2002 Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of Hoxa9, Hoxa7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of Hoxa9 and Meis1. Oncogene 102 12082612
2010 Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1. Proceedings of the National Academy of Sciences of the United States of America 101 20498086
1999 The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and is recurrent in T-cell acute lymphocytic leukemia. Blood 81 10477737
2004 Differential and common leukemogenic potentials of multiple NUP98-Hox fusion proteins alone or with Meis1. Molecular and cellular biology 80 14966272
2001 The nucleoporin Nup98 associates with the intranuclear filamentous protein network of TPR. Proceedings of the National Academy of Sciences of the United States of America 79 11248057
2006 The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions. Immunity 78 16546098
2004 The role of NUP98 gene fusions in hematologic malignancy. Leukemia & lymphoma 78 15359631
2001 NUP98 gene fusions in hematologic malignancies. Leukemia 76 11681408
2003 Sec13 shuttles between the nucleus and the cytoplasm and stably interacts with Nup96 at the nuclear pore complex. Molecular and cellular biology 75 14517296
2017 Nup98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells. Genes & development 73 29269482
2014 NUP98-PHF23 is a chromatin-modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD histone reader function. Cancer discovery 73 24535671
2010 The mobile FG nucleoporin Nup98 is a cofactor for Crm1-dependent protein export. Molecular biology of the cell 70 20375145
2020 CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia. Blood 69 32344427
2006 Pervasive adaptive evolution among interactors of the Drosophila hybrid inviability gene, Nup96. Molecular biology and evolution 69 17056646
2016 Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes. eLife 67 26740045
2012 Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription. PLoS pathogens 67 23028327
2003 The oncogene Nup98-HOXA9 induces gene transcription in myeloid cells. The Journal of biological chemistry 66 14561764
2023 Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haematologica 64 36815378
2008 Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood 64 18388181
2020 Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex. Biochemical and biophysical research communications 63 33360543
2006 Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation. Cancer research 63 17178874
2002 The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15). Cancer research 63 11782354
2002 Single-translocation and double-chimeric transcripts: detection of NUP98-HOXA9 in myeloid leukemias with HOXA11 or HOXA13 breaks of the chromosomal translocation t(7;11)(p15;p15). Blood 63 11830496
2014 Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1 • Nup98). Proceedings of the National Academy of Sciences of the United States of America 61 24927547
2007 Retroviral insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation. Cancer research 61 17545593
2011 NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis. British journal of haematology 60 21810091
2007 NUP98 dysregulation in myeloid leukemogenesis. Annals of the New York Academy of Sciences 59 17442773
2001 NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia. Genes, chromosomes & cancer 55 11241795
2012 Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes. Molecular cell 54 23102701
2018 Dasatinib and navitoclax act synergistically to target NUP98-NSD1+/FLT3-ITD+ acute myeloid leukemia. Leukemia 52 30568173
2010 Effects of the NUP98-DDX10 oncogene on primary human CD34+ cells: role of a conserved helicase motif. Leukemia 50 20339440
2006 The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia. Blood 50 16861351
2014 Potent co-operation between the NUP98-NSD1 fusion and the FLT3-ITD mutation in acute myeloid leukemia induction. Haematologica 49 24951466
2003 Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13). Genes, chromosomes & cancer 49 12461755
2010 Nucleoporin Nup98: a gatekeeper in the eukaryotic kingdoms. Genes to cells : devoted to molecular & cellular mechanisms 43 20545767
2007 Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12). British journal of haematology 43 17233820
2011 RNA export factor RAE1 contributes to NUP98-HOXA9-mediated leukemogenesis. Cell cycle (Georgetown, Tex.) 42 21467841
2005 NUP98 fusion in human leukemia: dysregulation of the nuclear pore and homeodomain proteins. International journal of hematology 42 16105755
2004 NUP98-topoisomerase I acute myeloid leukemia-associated fusion gene has potent leukemogenic activities independent of an engineered catalytic site mutation. Blood 41 15100157
2003 The SONB(NUP98) nucleoporin interacts with the NIMA kinase in Aspergillus nidulans. Genetics 40 14668365
2020 Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia. Cancers 39 32993115
2001 Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation. BMC genetics 38 11737860
2014 Critical role of retinoid/rexinoid signaling in mediating transformation and therapeutic response of NUP98-RARG leukemia. Leukemia 37 25510432
2023 The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML. HemaSphere 35 37520776
2000 Heterogenous fusion transcripts involving the NUP98 gene and HOXD13 gene activation in a case of acute myeloid leukemia with the t(2;11)(q31;p15) translocation. Leukemia 35 10995009
2015 Epigenetic therapy restores normal hematopoiesis in a zebrafish model of NUP98-HOXA9-induced myeloid disease. Leukemia 34 26017032
2017 Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9. eLife 33 28221134
2010 Nup98-homeodomain fusions interact with endogenous Nup98 during interphase and localize to kinetochores and chromosome arms during mitosis. Molecular biology of the cell 32 20237156
2022 SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation. Journal of experimental & clinical cancer research : CR 31 35073946
2017 MLL is essential for NUP98-HOXA9-induced leukemia. Leukemia 31 28210005
2008 NUP98-HOX translocations lead to myelodysplastic syndrome in mice and men. Journal of the National Cancer Institute. Monographs 31 18648006
2016 Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype. PloS one 29 27031510
2007 A new fusion gene NUP98-IQCG identified in an acute T-lymphoid/myeloid leukemia with a t(3;11)(q29q13;p15)del(3)(q29) translocation. Oncogene 29 18084320
2019 Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities. Blood advances 28 31698461
2010 NUP98-MLL fusion in human acute myeloblastic leukemia. Blood 27 20558618
2013 NUP98 fusion oncoproteins promote aneuploidy by attenuating the mitotic spindle checkpoint. Cancer research 26 24371226
1999 The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts. International journal of hematology 26 10222653
2018 NUP98-BPTF gene fusion identified in primary refractory acute megakaryoblastic leukemia of infancy. Genes, chromosomes & cancer 25 29427526
2020 Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion. Nature communications 24 32620764
2024 Combination of menin and kinase inhibitors as an effective treatment for leukemia with NUP98 translocations. Leukemia 22 38890447
2013 Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking. Biochemical and biophysical research communications 22 23541576
2009 A NUP98-HOXD13 fusion gene impairs differentiation of B and T lymphocytes and leads to expansion of thymocytes with partial TCRB gene rearrangement. Journal of immunology (Baltimore, Md. : 1950) 22 19841179
2020 Acute Myeloid Leukemia with NUP98-RARG Gene Fusion Similar to Acute Promyelocytic Leukemia: Case Report and Literature Review. OncoTargets and therapy 21 33116634
2016 Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis. Frontiers in cellular and infection microbiology 20 28018858
2025 The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators. Molecular cell 19 39922194
2019 NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis. Blood advances 19 30944097
2008 Leukemogenic properties of NUP98-PMX1 are linked to NUP98 and homeodomain sequence functions but not to binding properties of PMX1 to serum response factor. Oncogene 18 18604245
2009 Acute myeloid leukemia with NUP98-HOXC13 fusion and FLT3 internal tandem duplication mutation: case report and literature review. Cancer genetics and cytogenetics 17 19665070
2025 KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia. Cancer discovery 16 40536430
2024 NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities. HemaSphere 16 39323480
2016 Human NUP98-HOXA9 promotes hyperplastic growth of hematopoietic tissues in Drosophila. Developmental biology 16 27838340
2015 NUP98/11p15 translocations affect CD34+ cells in myeloid and T lymphoid leukemias. Leukemia research 16 26004809
2011 Functional analysis of the NUP98-CCDC28A fusion protein. Haematologica 15 22058212
2023 Novel NUP98::ASH1L Gene Fusion in Acute Myeloid Leukemia Detected by Optical Genome Mapping. Cancers 14 37296904
2022 Nup98-dependent transcriptional memory is established independently of transcription. eLife 14 35289742
2019 NUP98 - a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer. BMC cancer 14 30935371
2023 Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML. European journal of haematology 13 37465857
2005 Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro. Acta pharmacologica Sinica 13 16174445
2025 Precision medicine for high-risk gene fusions in pediatric AML: a focus on KMT2A, NUP98, and GLIS2 rearrangements. Blood 12 39808803

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