Affinage

NUP214

Nuclear pore complex protein Nup214 · UniProt P35658

Length
2090 aa
Mass
213.6 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 41 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

NUP214 (CAN) is an essential FG-repeat nucleoporin on the cytoplasmic face of the nuclear pore complex (NPC) whose loss arrests cells in G2 and blocks both NLS-mediated protein import and poly(A)+ mRNA export, rendering it required for viability (PMID:8896451). Structurally it comprises an N-terminal seven-bladed β-propeller domain (PMID:17264208) and an extended C-terminal FG-repeat region, and it forms an interdependent subcomplex with Nup88 that in turn anchors Nup358 at the NPC (PMID:9049309, PMID:14993277). Its central function is to provide a terminal, high-affinity docking platform for the export receptor CRM1/XPO1: a structurally defined array of FG motifs engages eight sites on CRM1, clamping it in a closed conformation to stabilize RanGTP-containing export complexes (PMID:26489467, PMID:23264634), and depletion of the Nup214–Nup88 module selectively impairs CRM1-mediated export of NES cargoes, HIV-Rev, and the 60S preribosomal subunit while sparing import (PMID:16943420, PMID:16675447). At the same cytoplasmic face NUP214 binds the DEAD-box helicase DDX19/DBP5 through its N-terminal domain in a manner mutually exclusive with RNA, inhibiting DBP5 ATPase and RNA-binding activity and thereby resetting the helicase to drive directional mRNP remodeling and mRNA release (PMID:19219046, PMID:19208808). Through these export and shuttling activities NUP214 also modulates signaling, controlling nucleocytoplasmic distribution of Smad2 and of the Notch effector RBP-J (PMID:12191473, PMID:31186352), and it serves as a direct NPC docking receptor for incoming adenovirus and herpesvirus capsids during viral genome import (PMID:11781571, PMID:25410864, PMID:19386703). Biallelic loss-of-function variants in NUP214 cause an acute febrile encephalopathy, with patient fibroblasts showing reduced NUP214/NUP88, impaired transport, plugged NPC channels, and increased apoptosis (PMID:31178128). Chromosomal rearrangements fuse NUP214 to SET, DEK, SQSTM1, or ABL1 in leukemia: the nucleoporin-fusion proteins tether CRM1/XPO1 onto chromatin to drive aberrant HOX-cluster transcription (PMID:18299449, PMID:31755865, PMID:32343715, PMID:40148556, PMID:40204893), while NUP214-ABL1 is a constitutively active, NPC-localized tyrosine kinase whose transforming activity depends on its pore localization (PMID:18614052, PMID:15361874).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Established that NUP214 is not a passive scaffold but is essential for the core NPC functions of cell-cycle progression and bidirectional nucleocytoplasmic transport.

    Evidence CAN-/- mouse embryo and ES cell knockout with cell-cycle, NLS-import, and poly(A)+ RNA readouts

    PMID:8896451

    Open questions at the time
    • Did not resolve which molecular partner mediates each transport defect
    • Did not distinguish direct transport roles from secondary cell-cycle effects
  2. 1997 High

    Defined NUP214 as the organizer of a cytoplasmic-face subcomplex containing Nup88 and CRM1, showing Nup88 NPC localization depends on NUP214 and that NUP214's FG region carries the CRM1-interaction domain.

    Evidence Reciprocal Co-IP, immunofluorescence, knockout embryos, and dominant-negative overexpression

    PMID:9049309

    Open questions at the time
    • Structural basis of FG–CRM1 recognition not yet defined
    • Functional consequence of CRM1 docking on export not directly measured
  3. 2002 High

    Linked NUP214 export function to signaling by showing it binds Smad2 and competes with cytoplasmic/nuclear retention factors to mediate constitutive Smad2 shuttling.

    Evidence Co-IP, pulldown, competition binding, and shuttling assays

    PMID:12191473

    Open questions at the time
    • Did not test whether Smad2 shuttling alters TGFβ transcriptional output in vivo
    • Relative contribution of NUP214 vs Nup153 unresolved
  4. 2004 High

    Positioned NUP214 within the cytoplasmic filament architecture, showing it and Nup88 are mutually interdependent and together anchor Nup358 at the NPC.

    Evidence RNAi depletion with localization readouts and Co-IP

    PMID:14993277

    Open questions at the time
    • Stoichiometry of the Nup214–Nup88–Nup358 assembly not determined
  5. 2006 High

    Demonstrated that the Nup214–Nup88 module is a terminal high-affinity binding site that is specifically required for CRM1-mediated export, including of 60S preribosomal subunits, while import is spared.

    Evidence RNAi with transport-factor export assays, biochemical reconstitution of Nup214–CRM1–RanGTP–cargo complex, and coiled-coil domain rescue

    PMID:16675447 PMID:16943420

    Open questions at the time
    • How cargo is handed off from NUP214 to release into the cytoplasm not resolved
    • FG-domain accessibility paradox (large FG domain not freely accessible) not mechanistically explained
  6. 2009 High

    Resolved how NUP214 controls mRNP remodeling by structurally and biochemically showing it binds DBP5/DDX19 mutually exclusively with RNA and inhibits its ATPase, resetting the helicase for directional mRNA release.

    Evidence Crystal structures of DBP5–RNA/AMPPNP and DBP5–Nup214 (N-terminal domain), plus in vitro ATPase and RNA-binding assays

    PMID:19208808 PMID:19219046

    Open questions at the time
    • In-cell kinetics of the proposed ratchet/reset cycle not directly observed
    • Coordination between DBP5 regulation and CRM1 docking at the same pore face unclear
  7. 2015 High

    Provided the atomic mechanism of NUP214 export function: FG motifs occupy eight sites on CRM1 and clamp it in a closed conformation to stabilize the export complex.

    Evidence Crystal structure of Nup214 FG fragment with CRM1–Snurportin1–RanGTP plus mutagenesis and cell-based export assays

    PMID:26489467

    Open questions at the time
    • How clamping is released to permit cargo dissociation not defined
    • Which individual FG sites are rate-limiting in cells not established
  8. 2014 High

    Confirmed NUP214 as a direct NPC receptor for viral capsids by mapping the adenovirus hexon binding site to a defined N-terminal segment required for viral genome import.

    Evidence RNAi depletion, in vitro hexon-binding in permeabilized cells, domain rescue, and infection assays (building on earlier adenovirus and HSV-1 capsid docking studies)

    PMID:11781571 PMID:19386703 PMID:25410864

    Open questions at the time
    • Whether the N-terminal capsid-binding role conflicts with normal transport functions not addressed
    • Generality across other viruses limited
  9. 2019 High

    Connected NUP214 loss-of-function to human Mendelian disease and extended its signaling role, defining acute febrile encephalopathy from biallelic variants and a role in negatively regulating Notch via RBP-J export.

    Evidence Patient fibroblast transport assays, SEM of NPC channels, and apoptosis assays; separately reporter assays, ChIP-qPCR, and zebrafish for Notch/RBP-J

    PMID:31178128 PMID:31186352

    Open questions at the time
    • Tissue-specificity of encephalopathy phenotype not mechanistically explained
    • Whether RBP-J is a direct CRM1 cargo of NUP214 not structurally shown
  10. 2008 High

    Defined two distinct oncogenic logics of NUP214 fusions: NPC-localization-dependent constitutive ABL1 kinase activity, and SET-NUP214-driven transcriptional activation of HOXA genes via CRM1/DOT1L.

    Evidence Localization and transformation assays for NUP214-ABL1; ChIP, siRNA, and Co-IP for SET-NUP214; episomal-amplification genetics establishing the NUP214-ABL1 fusion

    PMID:15361874 PMID:18299449 PMID:18614052 PMID:18784740

    Open questions at the time
    • Why NPC localization is required for ABL1 transformation mechanistically unresolved
    • How the chimeras recruit transcriptional machinery to HOX chromatin not fully defined
  11. 2025 High

    Consolidated the export-receptor-hijack model of nucleoporin fusions, showing SET/DEK/SQSTM1-NUP214 tether CRM1/XPO1 onto HOX and FOXC1 chromatin to drive leukemogenic transcription, with XPO1 as a therapeutic dependency.

    Evidence FG-motif mutagenesis with mouse transplant and ChIP; CRM1/XPO1 inhibition and ChIP-seq/CUT&RUN with transcriptomics and PDX models

    PMID:27114368 PMID:27613868 PMID:31755865 PMID:32343715 PMID:40148556 PMID:40204893

    Open questions at the time
    • How the fusion reverses CRM1 from an exporter into a chromatin-tethering factor not fully explained
    • Contribution of fusion-specific partner domains (SET vs DEK vs SQSTM1) to target selectivity incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how NUP214 coordinates its multiple concurrent activities at a single pore face — CRM1 docking, DBP5 resetting, capsid receptor, and partner anchoring — and how its own NES-dependent targeting is integrated with these roles.
  • No integrated in-cell model coordinating export, mRNP remodeling, and viral docking
  • Mechanism translating NUP214 loss into specific neurological versus hematopoietic phenotypes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3
Partners
DDX19/DBP5NUP358NUP62NUP84NUP88RBPJSMAD2XPO1/CRM1
Complex memberships
CRM1–RanGTP–cargo export complexNup214–Nup88 nucleoporin subcomplexnuclear pore complex (cytoplasmic face)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CAN/Nup214 forms a dynamic subcomplex at the nuclear pore complex with Nup88 and human CRM1 (hCRM1). Depletion of CAN from the NPC causes concomitant loss of Nup88, indicating Nup88 NPC localization depends on CAN binding. The FG-repeat region of CAN contains the hCRM1-interaction domain; nuclear overexpression of this region depletes hCRM1 from the NPC. Co-immunoprecipitation, immunofluorescence, CAN knockout mouse embryos, dominant-negative overexpression The EMBO journal High 9049309
1996 CAN/Nup214 is essential for cell cycle progression and nucleocytoplasmic transport in vivo. CAN-/- mouse embryos arrest in G2 phase upon depletion of maternally derived CAN, accompanied by inhibition of NLS-mediated nuclear protein import and nuclear accumulation of poly(A)+ RNA (mRNA export block). CAN-/- ES cells are not viable. Genetic knockout (CAN-/- mouse embryos and ES cells), in vitro culture, immunofluorescence for cell cycle markers and NLS-import, in situ hybridization for poly(A)+ RNA The EMBO journal High 8896451
2009 DBP5/DDX19 binds NUP214 in a manner mutually exclusive with RNA binding. Crystal structures of human DBP5 bound to RNA/AMPPNP and to NUP214 show overlapping binding surfaces. NUP214 decreases both RNA-binding and ATPase activities of DBP5 in vitro, suggesting NUP214 acts as a negative regulator that resets DBP5 at the cytoplasmic face of the NPC for mRNA release. Crystal structure determination, in vitro ATPase assay, in vitro RNA-binding assay Nature structural & molecular biology High 19219046
2009 Crystal structure of the Nup214 N-terminal domain in complex with the DEAD-box helicase Ddx19 (ADP-bound state) at 2.5 Å resolution reveals that interaction surfaces are evolutionarily conserved and have strongly opposing surface potentials (helicase surface positive, Nup214 surface negative), suggesting a ratchet mechanism for mRNP remodeling during nuclear export. X-ray crystallography Proceedings of the National Academy of Sciences of the United States of America High 19208808
2007 Crystal structure of the human Nup214 N-terminal domain at 1.65 Å resolution reveals a seven-bladed β-propeller followed by a 30-residue C-terminal extended peptide that folds back onto the β-propeller bottom face, with a proposed role for the C-terminal peptide extension in NPC assembly. X-ray crystallography Proceedings of the National Academy of Sciences of the United States of America High 17264208
2015 Crystal structure of a 117-amino-acid FG-repeat fragment of Nup214 in complex with CRM1, Snurportin1, and RanGTP at 2.85 Å resolution reveals eight binding sites for Nup214 FG motifs on CRM1. Nup214 binds to both N- and C-terminal regions of CRM1, clamping it in a closed conformation and stabilizing the export complex. Conserved hydrophobic pockets on CRM1 are required for FG-motif recognition, validated by biochemical and cell-based assays. X-ray crystallography, in vitro binding assays, cell-based export assays, mutagenesis of FG motifs Cell reports High 26489467
2002 Smad2 directly interacts with NUP214/CAN and Nup153 to mediate constitutive nucleocytoplasmic shuttling. CAN/Nup214 and Nup153 compete with the cytoplasmic retention factor SARA and the nuclear partner FAST-1 for binding to a hydrophobic corridor on the MH2 surface of Smad2. TGFβ receptor phosphorylation modifies Smad2 affinity for SARA and Smad4 but not for CAN/Nup214 or Nup153. Co-immunoprecipitation, pulldown assays, shuttling assays, competition binding assays Molecular cell High 12191473
2006 Depletion of Nup214/Nup88 by RNAi in human cells leads to strongly reduced CRM1-mediated nuclear export of NFAT and HIV-Rev, while nuclear protein import and mRNA export are largely unaffected. A high-affinity complex containing Nup214, CRM1, RanGTP, and export cargo is biochemically characterized, supporting a model where Nup214/Nup88 provides a terminal high-affinity binding site for CRM1 during export. RNAi depletion, nuclear export assays (shuttling transcription factors, HIV-Rev), biochemical complex reconstitution Molecular and cellular biology High 16943420
2004 Nup88 localizes between Nup358 and Nup214 at the cytoplasmic NPC face and physically interacts with both. RNAi depletion of either Nup88 or Nup214 causes strong reduction of Nup358 at the nuclear envelope, demonstrating that Nup88 and Nup214 mediate the attachment of Nup358 to the NPC. Nup88 and Nup214 are interdependent at the NPC and are not affected by absence of Nup358. RNAi, immunofluorescence, Co-immunoprecipitation Molecular and cellular biology High 14993277
2006 Depletion of the Nup214-Nup88 nucleoporin subcomplex by RNAi causes a dramatic defect in CRM1-mediated nuclear export of the 60S preribosomal subunit (via NMD3 adaptor). The coiled-coil region of Nup214 (not the FG-repeat domain) is sufficient for rescuing 60S export, coinciding with recruitment of Nup88. The large FG domain of Nup214 is not accessible to freely diffusing nuclear molecules. RNAi depletion, fluorescence microscopy export assays, domain-rescue experiments The Journal of biological chemistry High 16675447
2001 CAN/Nup214 is a docking site for incoming adenovirus type 2 (Ad2) capsids at the NPC. Capsid binding to CAN is independent of cytosolic factors. Capsid disassembly at the NPC requires nuclear histone H1 binding to stably docked capsids, involving H1-import factors, thereby restricting irreversible DNA release to NPC proximity. Immunofluorescence, biochemical binding assays, histone H1 depletion/addition experiments Nature cell biology High 11781571
2014 The N-terminal domain of Nup214 (specifically a 137-amino-acid segment) is the direct NPC binding site for adenovirus hexon protein. RNAi depletion of Nup214 (but not Nup358) strongly reduces hexon binding and nuclear import of viral DNA. Expression of an NPC-targeted N-terminal Nup214 domain in Nup214-depleted cells restores hexon binding and viral genome import. RNAi depletion, in vitro hexon-binding assay in digitonin-permeabilized cells, domain-rescue experiments, viral infection assay Journal of virology High 25410864
2009 Herpes simplex virus type 1 (HSV-1) capsids interact with CAN/Nup214 in infected cells. RNA silencing of CAN/Nup214 delays the onset of viral DNA replication in the nucleus. The minor capsid protein pUL25 directly interacts with CAN/Nup214 and nucleoporin hCG1, identifying CAN/Nup214 as a nuclear receptor for herpesvirus capsids and pUL25 as the interface between incoming capsids and the NPC. Co-immunoprecipitation, RNAi silencing, viral DNA replication assay Journal of virology Medium 19386703
1999 HIV-1 Rev can recruit Nup98 and Nup214 (but not Nup153) to the nucleolus in HeLa cells. The FG-containing repeat domains of Nup98 and Nup214 (but not Nup153) competitively inhibit Rev/RRE-mediated HIV gene expression, demonstrating direct participation of Nup214 in CRM1-mediated Rev nuclear export. Immunofluorescence (recruitment to nucleolus), competition inhibition assay with isolated FG domains Journal of virology Medium 9847314
1998 Overexpression of CAN/Nup214 in U937 cells causes G0 arrest, nuclear mRNA accumulation, and apoptosis. Overexpression of the C-terminal FG-repeat region alone sequesters hCRM1 in the nucleoplasm (and importin beta/p97 from the NPC), which is sufficient to inhibit cell growth and induce apoptosis, confirming that CAN's FG region interacts with hCRM1 and that this interaction is functionally critical. Overexpression in myeloid cell lines, flow cytometry (cell cycle), in situ hybridization (mRNA export), immunofluorescence (hCRM1, p97 localization) Molecular and cellular biology Medium 9488438
1997 Nup84 (a novel non-glycosylated nucleoporin) is tightly associated with CAN/Nup214 and co-localizes on the cytoplasmic face of the NPC. Mutagenesis shows the coiled-coil C-terminal domain of Nup84 is required for NPC association, while the N-terminal region contains the CAN/Nup214 interaction site. Nup84 may anchor CAN/Nup214 to the central NPC framework. Co-immunoprecipitation, immunofluorescence/electron microscopy, domain mutagenesis and expression The Journal of cell biology Medium 9166401
2012 Multiple specific phenylalanine-glycine (FG) motifs in the C-terminal repeat region of Nup214 are essential for CRM1 binding. Dominant-negative Nup214 FG fragments inhibit CRM1-dependent nuclear export but do not affect several nuclear import pathways, revealing a specific role for Nup214 FG repeats in export. Mutagenesis of FG motifs, dominant-negative inhibition assays, nuclear export assays in cells The Journal of biological chemistry Medium 23264634
2008 SET-NUP214 fusion protein binds to promoter regions of specific HOXA genes where it interacts with CRM1 and DOT1L, transcriptionally activating HOXA cluster members. siRNA knockdown of SET-NUP214 abolishes HOXA gene expression, inhibits proliferation, and induces differentiation in LOUCY T-ALL cells. ChIP, siRNA knockdown, gene expression analysis, Co-immunoprecipitation Blood Medium 18299449
2008 NUP214-ABL1 fusion protein localizes to the nuclear pore complex, and this NPC localization is required for its transforming potential. NUP214-ABL1 has attenuated transforming capacity compared to BCR-ABL1, preferentially transforms T cells, lacks activation loop phosphorylation, and differs from BCR-ABL1 in kinase activity initiation and downstream signaling. Subcellular localization (immunofluorescence), transformation assays (mouse bone marrow transplant, cell line), domain analysis Molecular cell High 18614052
2008 NUP214-ABL1 has lower in vitro tyrosine kinase activity than BCR-ABL1, lacks activation loop phosphorylation, is more sensitive to imatinib in vitro and in cells, and phosphorylates a different spectrum of substrate peptides. Src kinases (including LCK) are differentially involved in NUP214-ABL1 downstream signaling compared to BCR-ABL1. In vitro kinase assay, Western blot for phosphorylation, imatinib sensitivity assay, peptide array substrate profiling Leukemia Medium 18784740
2004 NUP214-ABL1 fusion is formed by extrachromosomal (episomal) amplification of a 500-kb region of chromosome 9q34 containing ABL1 and NUP214, generating a constitutively phosphorylated tyrosine kinase sensitive to imatinib. The rearrangement is associated with increased HOX expression and CDKN2A deletion. Molecular analysis (RT-PCR, FISH, cytogenetics), Western blot for constitutive phosphorylation, imatinib sensitivity assay Nature genetics High 15361874
2016 SET-Nup214 and DEK-Nup214 fusion proteins interact with XPO1/CRM1 and NXF1/TAP. They decrease XPO1-mediated nuclear export of NES proteins (cyclin B, NF-κB pathway components) by tethering XPO1 onto nuclear dots where fusion proteins localize, and inhibit NF-κB-mediated transcription by abnormally trapping the p65/IκB complex in the nucleus. Co-immunoprecipitation, immunofluorescence, nuclear export assays, NF-κB reporter assay Molecular and cellular biology Medium 27114368
2016 SET-Nup214 forms dynamic nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins, inhibiting both nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214 also forms nuclear bodies and inhibits nuclear protein but NOT poly(A)+ RNA export. The interaction of both fusion proteins with CRM1 is RanGTP-dependent. The Nup214 portion mediates export inhibition while the SET/SQSTM1 portion determines localization and extent of the effect. Co-immunoprecipitation, fluorescence microscopy (live imaging, FRAP), nuclear export assays, binding assays The Journal of biological chemistry Medium 27613868
2019 CRM1 accumulates at HOX cluster chromatin regions and recruits SET-Nup214 and NPM1c to HOX cluster regions, leading to HOX gene activation. CRM1 inhibition disperses this recruitment and suppresses HOX gene expression in leukemia cells. SET-Nup214 recruitment to HOX genes requires nucleoporin-CRM1 interaction. ChIP-seq, CRM1 inhibitor treatment, siRNA knockdown, gene expression analysis eLife Medium 31755865
2013 LCK kinase activity is absolutely required for proliferation and survival of NUP214-ABL1-positive T-ALL cells. Mass spectrometry identifies NUP214-ABL1 interaction partners MAD2L1, NUP155, and SMC4 as required for proliferation and survival of NUP214-ABL1-positive cells. The NUP214-ABL1 signaling network is distinct from BCR-ABL1. Kinase inhibitor assays (LCK inhibitors, dasatinib, bosutinib), siRNA knockdown of interactors, mass spectrometry interactome Haematologica Medium 23872305
2006 In Drosophila, Nup214 binds CRM1 directly and anchors it to the nuclear envelope. In nup214 mutants, CRM1 accumulates in the nucleus and NES-protein export is enhanced. The Nup214-Nup88 complex sequesters CRM1 at the nuclear rim; Nup214 protects Nup88 from degradation while Nup88 is sufficient for targeting the complex to nuclear pores. The NFκB transcription factor Dorsal is a CRM1 substrate requiring Nup214 for nuclear translocation upon signaling. Genetic mutant analysis (Drosophila nup214 mutants), co-immunoprecipitation, immunofluorescence, overexpression Journal of cell science Medium 17032737
2007 In Drosophila, RNAi inactivation reveals that the FG repeats of Nup153 are necessary for its import function while Nup214 FG region has an antagonistic relationship with RanBP3 in determining CRM1 localization and nuclear protein export. Nup214 FG region and RanBP3 have opposing effects on CRM1 nuclear accumulation and export efficiency. RNAi in Drosophila S2 cells, nuclear import/export assays The Journal of cell biology Medium 17682050
2004 Tristetraprolin (TTP) directly associates with the FG-repeat region of Nup214. Full-length Nup214 co-precipitates with TTP from intact cells. The interaction requires two intact zinc fingers of TTP. A TTP mutant unable to bind Nup214 localizes throughout the cell rather than primarily in the cytosol, suggesting the Nup214 interaction regulates TTP localization. Yeast two-hybrid screen, co-immunoprecipitation from intact THP-1 cells, immunofluorescence Biochemical and biophysical research communications Low 14766228
2019 Biallelic pathogenic variants in NUP214 in patients with acute febrile encephalopathy reduce NUP214 and NUP88 protein levels in primary fibroblasts, impair classical protein import and mRNA export, and cause a large increase in 'plugged' (central particle-containing) nuclear pore channels by scanning electron microscopy. Fibroblasts from affected individuals show delayed heat-shock stress response and surge in apoptotic cell death. Patient-derived fibroblasts, nuclear transport assays, scanning electron microscopy of NPC surface, immunoblotting, apoptosis assay American journal of human genetics High 31178128
2019 Nup214 and its partner Nup88 negatively regulate Notch signaling in mammalian cells and in vivo in zebrafish. Loss of Nup88/214 inhibits nuclear export of RBP-J (the DNA-binding component of the Notch pathway), increasing RBP-J binding to cognate promoter regions and enhancing downstream Notch signaling. Nuclear RBP-J levels are rate-limiting for Notch signaling. Reporter gene assays, immunocytochemistry, ChIP-qPCR, zebrafish in vivo experiments, siRNA knockdown The Journal of biological chemistry Medium 31186352
2021 Nup214 contains a classical nuclear export sequence (NES) that mediates Ran-dependent binding to CRM1. Mutations in the NES, or CRM1 inhibition with leptomycin B, cause nuclear accumulation of overexpressed Nup214. The NES function is required for correct cytoplasmic NPC targeting of Nup214 and for co-recruitment of binding partners Nup62 and Nup88 to the correct NPC location. NES mutagenesis, leptomycin B treatment, immunofluorescence, co-localization of binding partners Journal of cell science Medium 33589493
2008 DEK-NUP214 expression in myeloid cell lines causes a substantial increase in global protein synthesis via increased translation, not transcription. This is myeloid-lineage specific. DEK-NUP214 expression correlates with phosphorylation of translation initiation factor EIF4E. Global translation assay (metabolic labeling), Western blot for EIF4E phosphorylation, lineage-specificity testing in myeloid vs. non-myeloid cells Genes, chromosomes & cancer Medium 18181180
2013 DEK-NUP214 expression in myeloid cell lines increases cellular proliferation through upregulation of mTOR, with elevated mTORC1 (but not mTORC2) activity as measured by p70 S6 kinase phosphorylation. This increases protein synthesis and shifts metabolism toward oxidative phosphorylation. The mTORC1 inhibitor everolimus selectively reverses DEK-NUP214-induced proliferation. Western blot (mTOR, p70S6K, Akt phosphorylation), global translation assay, metabolic assay (lactate production, glucose consumption), mTOR inhibitor treatment BMC cancer Medium 24073922
2009 CAN/Nup214 interacts with the vitamin D receptor (VDR) via the carboxy-terminal FG-repeat-containing region of Nup214. Overexpression of full-length Nup214 facilitates VDR-mediated transactivation, while expression of the carboxy-terminal fragment (which competes with full-length Nup214 for VDR binding) suppresses it. The DNA-binding domain of VDR is required for Nup214-facilitated transactivation. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, transactivation reporter assay, domain deletion mapping Journal of cellular biochemistry Low 19229862
2015 Inhibition of NUP214 expression by miR-133b (validated by luciferase reporter assay) or direct siRNA knockdown elevates mitotic indices, delays degradation of mitotic markers cyclinB1 and cyclinA and H3 dephosphorylation, and causes chromosomal abnormalities and apoptosis, indicating a role for NUP214 in mitotic timing. miR-133b transfection, siRNA knockdown, luciferase reporter assay, flow cytometry (cell cycle), immunofluorescence (mitotic markers), video microscopy Molecular cancer Medium 25743594
2020 Influenza A NS2/NEP protein interacts with the amino-terminal FG domain of human Nup214 (identified by yeast two-hybrid, confirmed in yeast and mammalian cells). Nup214 knockdown suppresses influenza viral replication, indicating that Nup214 FG-domain interaction with NS2 is functionally important for viral vRNA export. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, Nup214 knockdown with viral replication assay Turkish journal of biology Low 32256144
2021 SET-NUP214 interacts with MLL (Mixed Lineage Leukemia) via the SET acidic region, and SET-NUP214 and MLL cooperatively enhance HoxA10 gene promoter activity. Neither the SET nor the Nup214 region alone is sufficient for this transcriptional enhancement. Co-immunoprecipitation, luciferase reporter assay for HoxA10 promoter, domain deletion analysis Genes to cells Medium 34320268
2020 SQSTM1-NUP214 interaction with CRM1 is mediated by NUP214 FG motifs. Mutation of these FG motifs reduces CRM1 binding by >50% and abolishes leukemogenic transformation in vitro and in vivo (serial replating and mouse transplant). SQSTM1-NUP214 binds Hoxa and Meis1 gene chromatin via CRM1, and impaired CRM1 binding correlates with impaired binding to these gene loci. FG-motif mutagenesis, co-immunoprecipitation, serial replating assay, mouse bone marrow transplantation, chromatin immunoprecipitation (ChIP) PloS one High 32343715
2025 DEK::NUP214 co-localizes with XPO1 at chromatin, and XPO1 inhibition (eltanexor) disrupts this co-localization, reduces DEK::NUP214 chromatin binding, and downregulates DEK::NUP214 target genes (FOXC1, HOX genes). DEK::NUP214 directly binds promoters of FOXC1 and HOXA/B clusters (CUT&RUN), and XPO1 inhibition selectively reduces this binding in t(6;9) cells. FKH-1 cells show genetic dependency on XPO1. XPO1 deletion, pharmacological XPO1 inhibition, CUT&RUN chromatin binding, transcriptomics, patient-derived xenograft model Leukemia High 40148556 40204893
2008 SET-CAN/NUP214 transgenic expression under Gata1 hematopoietic regulatory control in mice causes anemia, thrombocytopenia, and splenomegaly, with impairment of erythroid, megakaryocytic, and B-cell differentiation. A high population of c-kit+Sca-1+Lin- cells appears in bone marrow, demonstrating that SET-CAN blocks the hematopoietic differentiation program. Transgenic mouse model, bone marrow analysis (flow cytometry), hematopoietic cell characterization Journal of cellular physiology Medium 17620317
2018 NUP214-ABL1 cooperates with TLX1 to drive T-ALL in a transgenic mouse model. STAT5 (downstream effector of NUP214-ABL1) and TLX1 co-bind poised enhancer regions and cooperatively activate expression of MYC and BCL2. This cooperative enhancer activation is required for leukemogenesis. Transgenic mouse model, ChIP-seq, ATAC-seq, RNA-seq, pharmacological inhibition (BET inhibitors, STAT5 inhibitors) Cancer cell High 30107177

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The hypoxic cell: a target for selective cancer therapy--eighteenth Bruce F. Cain Memorial Award lecture. Cancer research 529 10606224
1997 The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. The EMBO journal 411 9049309
2004 Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nature genetics 318 15361874
1995 Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer research 282 7850785
2001 Import of adenovirus DNA involves the nuclear pore complex receptor CAN/Nup214 and histone H1. Nature cell biology 240 11781571
2002 Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. Molecular cell 207 12191473
1998 Cain, a novel physiologic protein inhibitor of calcineurin. The Journal of biological chemistry 200 9660798
2008 The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia. Blood 184 18299449
2009 The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner. Nature structural & molecular biology 150 19219046
2004 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. Molecular and cellular biology 141 14993277
1999 Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev. Journal of virology 136 9847314
2006 Nup214 is required for CRM1-dependent nuclear protein export in vivo. Molecular and cellular biology 128 16943420
2009 Herpesvirus capsid association with the nuclear pore complex and viral DNA release involve the nucleoporin CAN/Nup214 and the capsid protein pUL25. Journal of virology 127 19386703
1985 Properties of antitumor anthracyclines and new developments in their application: Cain memorial award lecture. Cancer research 127 3864526
1996 G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214. The EMBO journal 115 8896451
1989 Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer research 111 2491747
2002 Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death. Proceedings of the National Academy of Sciences of the United States of America 110 12114545
1998 Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis. Molecular and cellular biology 101 9488438
1996 Beyond DNA cross-linking: history and prospects of DNA-targeted cancer treatment--fifteenth Bruce F. Cain Memorial Award Lecture. Cancer research 98 8971150
2015 Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export. Cell reports 91 26489467
1997 Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex. The Journal of cell biology 89 9166401
2009 Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19. Proceedings of the National Academy of Sciences of the United States of America 82 19208808
2006 Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export. The Journal of biological chemistry 74 16675447
2011 Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica 70 21880637
2008 Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia 70 18401417
2014 t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica 65 24441146
2019 Chromatin-bound CRM1 recruits SET-Nup214 and NPM1c onto HOX clusters causing aberrant HOX expression in leukemia cells. eLife 58 31755865
2008 Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia. Leukemia 58 18923437
2019 NUP214 in Leukemia: It's More than Transport. Cells 57 30669574
2014 Nuclear import of adenovirus DNA involves direct interaction of hexon with an N-terminal domain of the nucleoporin Nup214. Journal of virology 56 25410864
2000 The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis. The Journal of biological chemistry 55 10931822
2006 The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFkappaB activation in Drosophila. Journal of cell science 53 17032737
2008 Kinase activation and transformation by NUP214-ABL1 is dependent on the context of the nuclear pore. Molecular cell 51 18614052
2007 Distinct functions of the Drosophila Nup153 and Nup214 FG domains in nuclear protein transport. The Journal of cell biology 51 17682050
2018 Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214-ABL1/TLX1-Positive T Cell Acute Lymphoblastic Leukemia. Cancer cell 49 30107177
2007 Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN. Proceedings of the National Academy of Sciences of the United States of America 48 17264208
2009 SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines. Journal of hematology & oncology 46 19166587
2014 SET-NUP214 is a recurrent γδ lineage-specific fusion transcript associated with corticosteroid/chemotherapy resistance in adult T-ALL. Blood 44 24449214
2006 NUP214-ABL1 in adult T-ALL: the GMALL study group experience. Blood 43 16873673
2013 NUP214-ABL1-mediated cell proliferation in T-cell acute lymphoblastic leukemia is dependent on the LCK kinase and various interacting proteins. Haematologica 41 23872305
1995 Initiatives with platinum- and quinazoline-based antitumor molecules--Fourteenth Bruce F. Cain Memorial Award Lecture. Cancer research 41 7796401
2016 Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase. The Journal of antibiotics 40 27072286
2008 Intrinsic differences between the catalytic properties of the oncogenic NUP214-ABL1 and BCR-ABL1 fusion protein kinases. Leukemia 40 18784740
2014 NUP214 fusion genes in acute leukemia (Review). Oncology letters 39 25120641
2008 Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis. Genes, chromosomes & cancer 37 18181180
2013 Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR. BMC cancer 36 24073922
1998 Translational research: walking the bridge between idea and cure--seventeenth Bruce F. Cain Memorial Award lecture. Cancer research 36 9766639
2016 Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway. Molecular and cellular biology 33 27114368
2019 Pathogenic Variants in NUP214 Cause "Plugged" Nuclear Pore Channels and Acute Febrile Encephalopathy. American journal of human genetics 31 31178128
2015 Inhibition of nucleoporin member Nup214 expression by miR-133b perturbs mitotic timing and leads to cell death. Molecular cancer 31 25743594
2016 Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an immunocompromised mouse model. Oncogene 27 27065320
2012 Several phenylalanine-glycine motives in the nucleoporin Nup214 are essential for binding of the nuclear export receptor CRM1. The Journal of biological chemistry 27 23264634
2008 Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-Ibeta-CAN/Nup214. Journal of cellular physiology 27 17620317
2004 Direct association of tristetraprolin with the nucleoporin CAN/Nup214. Biochemical and biophysical research communications 23 14766228
1995 Molecular characterization of the food-borne fungus Neosartorya fischeri (Malloch and Cain). Applied and environmental microbiology 23 7747958
2016 Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia. Oncotarget 22 27821800
2011 Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del(9)(q34);SET-NUP214 rearrangement. Annals of hematology 22 21720744
2010 Molecular characterization of alternative SET-NUP214 fusion transcripts in a case of acute undifferentiated leukemia. Cancer genetics and cytogenetics 22 20682390
2010 The Cain and Abl of epithelial-mesenchymal transition and transforming growth factor-β in mammary epithelial cells. Cells, tissues, organs 22 21051857
2017 Dasatinib and chemotherapy in a patient with early T-cell precursor acute lymphoblastic leukemia and NUP214-ABL1 fusion: A case report. Experimental and therapeutic medicine 20 29067094
1997 The nucleoporin CAN/Nup214 binds to both the cytoplasmic and the nucleoplasmic sides of the nuclear pore complex in overexpressing cells. Experimental cell research 20 9141635
2016 The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export. The Journal of biological chemistry 19 27613868
2012 Nuclear distributions of NUP62 and NUP214 suggest architectural diversity and spatial patterning among nuclear pore complexes. PloS one 19 22558357
2020 Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission. British journal of haematology 18 32020596
2011 T-cell acute lymphoblastic leukemia associated with complex karyotype and SET-NUP214 rearrangement: a case study and review of the literature. Annals of clinical and laboratory science 16 22075511
2009 Calcineurin inhibitor protein (CAIN) attenuates Group I metabotropic glutamate receptor endocytosis and signaling. The Journal of biological chemistry 16 19717561
2021 Myelodysplastic syndrome with t(6;9)(p22;q34.1)/DEK-NUP214 better classified as acute myeloid leukemia? A multicenter study of 107 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 15 33558656
2015 The kinetics of relapse in DEK-NUP214-positive acute myeloid leukemia patients. European journal of haematology 15 25605311
2016 B-cell acute lymphoblastic leukemia associated with SET-NUP214 rearrangement: A case report and review of the literature. Oncology letters 14 27073532
2020 Interaction of influenza A virus NS2/NEP protein with the amino-terminal part of Nup214. Turkish journal of biology = Turk biyoloji dergisi 13 32256144
2020 Targeted CRM1-inhibition perturbs leukemogenic NUP214 fusion proteins and exerts anti-cancer effects in leukemia cell lines with NUP214 rearrangements. Oncotarget 12 32934780
1995 A minor tyrosine phosphorylation site located within the CAIN domain plays a critical role in regulating tissue-specific transformation by erbB kinase. Journal of virology 12 7815495
2018 A Cryptic NUP214-ABL1 Fusion in B-cell Precursor Acute Lymphoblastic Leukemia. Journal of pediatric hematology/oncology 10 29219890
2017 DEK-NUP214-Fusion Identified by RNA-Sequencing of an Acute Myeloid Leukemia with t(9;12)(q34;q15). Cancer genomics & proteomics 10 29109093
2021 t(5;12)(q31;p13)/ETV6::ACSL6 and t(6;9)(p23;q34)/DEK::NUP214 concurrence in acute myeloid leukemia: an unusual association of two rare abnormalities. Cancer genetics 9 34979355
2020 The SQSTM1-NUP214 fusion protein interacts with Crm1, activates Hoxa and Meis1 genes, and drives leukemogenesis in mice. PloS one 9 32343715
2021 A nuclear export sequence promotes CRM1-dependent targeting of the nucleoporin Nup214 to the nuclear pore complex. Journal of cell science 8 33589493
2021 SET-NUP214 Fusion Gene Involved Early T-Cell Precursor Acute Lymphoblastic Leukemia in Adult with B Marker Expression. International journal of general medicine 8 33658838
2021 Case Report: The First Report of NUP214-ABL1 Fusion Gene in Acute Myeloid Leukemia Patient Detected by Next-Generation Sequencing. Frontiers in oncology 8 34307175
2019 The nuclear pore proteins Nup88/214 and T-cell acute lymphatic leukemia-associated NUP214 fusion proteins regulate Notch signaling. The Journal of biological chemistry 8 31186352
2021 SET-NUP214 and MLL cooperatively regulate the promoter activity of the HoxA10 gene. Genes to cells : devoted to molecular & cellular mechanisms 7 34320268
2019 Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia. Cold Spring Harbor molecular case studies 7 30936193
2025 XPO1-dependency of DEK::NUP214 leukemia. Leukemia 6 40148556
2022 Chemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy. The oncologist 6 35641210
2012 [Expression of SET-NUP214 fusion gene in patients with T-cell acute lymphoblastic leukemia and its clinical significance]. Zhongguo shi yan xue ye xue za zhi 6 23114116
2008 Deguelin represses both the expression of nucleophosmin and some nucleoporins: Nup88 and Nup214 in Jurkat cells. Biological & pharmaceutical bulletin 6 18175937
2023 SET-CAN/NUP214 fusion gene in leukemia: general features and clinical advances. Frontiers in oncology 5 37909026
2022 Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion. Pathology oncology research : POR 5 36172171
2022 Blast phase of chronic myeloid leukemia with concurrent BCR::ABL1 and SET::NUP214: A report of two cases. Molecular carcinogenesis 5 36321418
2021 Determining the Appropriate Treatment for T-Cell Acute Lymphoblastic Leukemia With SET-CAN/NUP214 Fusion: Perspectives From a Case Report and Literature Review. Frontiers in oncology 5 33869055
2009 Oncogenic nucleoporin CAN/Nup214 interacts with vitamin D receptor and modulates its function. Journal of cellular biochemistry 5 19229862
2025 DEK::NUP214 acts as an XPO1-dependent transcriptional activator of essential leukemia genes. Leukemia 4 40204893
2025 DEK-NUP214 monitoring before and after allogeneic haematopoietic stem cell transplantation for acute myeloid leukemia: A report from the TROPHY study group. Journal of translational internal medicine 4 40861068
2023 The outcome of acute leukemia patients with SET-NUP214 fusion after allogeneic stem cell transplantation. Frontiers in oncology 4 37901324
2023 NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution. Annals of laboratory medicine 4 38145892
2021 Clinico-Hematological Profile and Copy Number Abnormalities in a Cohort of STIL-TAL1 and NUP214-ABL1 Positive Pediatric T-Cell Acute Lymphoblastic Leukemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 4 34744339
2017 A novel variant translocation (1;9)(p22;q34) resulting in a DEK/NUP214 fusion gene in a patient with acute myeloid leukemia: A case report. Oncology letters 4 29344131
2015 NUP214-RAC1 and RAC1-COL12A1 Fusion in Complex Variant Translocations Involving Chromosomes 6, 7 and 9 in an Acute Myeloid Leukemia Case with DEK-NUP214. Cytogenetic and genome research 4 26517539
2011 [Gene rearrangement pattern of immunoglobulin and T-cell receptor (Ig/TR) and its clinical characteristics in children with SET-NUP214 fusion gene-positive leukemia/lymphoma]. Zhongguo shi yan xue ye xue za zhi 4 22169284
2024 NUP214 fusion genes in acute leukemias: genetic characterization of rare cases. Frontiers in oncology 3 38571499

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