Affinage

NUP37

Nucleoporin Nup37 · UniProt Q8NFH4

Length
326 aa
Mass
36.7 kDa
Annotated
2026-06-10
8 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NUP37 is a structural nucleoporin that integrates directly into the heptameric Y-complex of the nuclear pore through binding to Nup120/160, where it docks near the bend of the L-shaped Nup120 subunit and stabilizes the relative orientation of its two domains adjacent to the ELYS-binding interface (PMID:22955883). Beyond its architectural role, NUP37 governs nuclear pore complex abundance and thereby nuclear size, a function placed under transcriptional control by ASCL1, which directly binds the NUP37 promoter to repress its expression during neuronal transdifferentiation (PMID:41759523). NUP37 protein levels are further set post-translationally: TRIM28 binds NUP37 and SUMOylates it at Lys114/118/246, blocking K27-linked polyubiquitination and proteasomal degradation to stabilize the protein (PMID:39294431). In cancer contexts, NUP37 acts as a pro-tumorigenic effector, interacting with YAP to enhance YAP-TEAD transcriptional signaling and driving hepatocellular carcinoma growth, migration, and invasion (PMID:29228669).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2012 High

    Established how NUP37 is built into the nuclear pore — defining it as a direct structural subunit of the Y-complex rather than a peripheral associate.

    Evidence X-ray crystallography of S. pombe Nup37-Nup120 subassembly with reconstitution and mutagenesis

    PMID:22955883

    Open questions at the time
    • Structure is from S. pombe; human Y-complex architecture not directly resolved here
    • Functional consequence of the Nup37-Nup120 interface for pore assembly in vivo not quantified
    • Does not address regulation of NUP37 abundance or its non-structural roles
  2. 2017 Medium

    Connected NUP37 to oncogenic transcription by showing it physically enhances YAP-TEAD signaling, moving it beyond a purely architectural role.

    Evidence Co-IP, knockdown/overexpression, growth/migration/invasion assays and mouse model in HCC

    PMID:29228669

    Open questions at the time
    • Direct vs indirect nature of the NUP37-YAP interaction not structurally resolved
    • Whether this depends on NUP37's nuclear pore role is unclear
    • Single-lab finding without reciprocal validation
  3. 2023 Low

    Placed NUP37 as a downstream effector of DEPDC1B/PI3K-AKT signaling in colorectal cancer via physical binding and epistasis rescue.

    Evidence Co-IP, siRNA knockdown, overexpression rescue, xenograft in CRC

    PMID:37203403

    Open questions at the time
    • Single Co-IP and epistasis rescue with limited mechanistic resolution
    • Mechanism linking NUP37 to PI3K/AKT activation not defined
    • Direct binding not independently confirmed
  4. 2024 Medium

    Identified the post-translational control of NUP37 stability — TRIM28-mediated SUMOylation antagonizes ubiquitin-driven degradation.

    Evidence Reciprocal Co-IP, site-specific SUMOylation mutagenesis (K114/118/246), ubiquitination assays, xenografts in HCC

    PMID:39294431

    Open questions at the time
    • E3 ligase responsible for K27-linked ubiquitination not identified
    • Whether SUMOylation affects NUP37's pore-assembly function unknown
    • Single-lab study
  5. 2024 Low

    Linked NUP37 to DNA methylation machinery, positioning it upstream of DNMT1 to drive glioma proliferation and invasion.

    Evidence Co-IP and DNMT1-overexpression rescue of NUP37 depletion in glioma cells

    PMID:39174498

    Open questions at the time
    • Single Co-IP and epistasis rescue with limited mechanistic detail
    • Mechanism by which NUP37 controls DNMT1 not defined
    • Direct interaction not reciprocally validated
  6. 2026 Medium

    Defined a transcriptional input controlling NUP37 levels and tied NUP37 dosage to nuclear pore abundance and nuclear size during cell-fate conversion.

    Evidence ASCL1 promoter-binding assay, bidirectional knockdown/overexpression, live-cell imaging of nuclear size in neuronal transdifferentiation

    PMID:41759523

    Open questions at the time
    • Mechanism coupling NUP37 dosage to NPC number and nuclear shrinkage not resolved
    • Generality beyond neuronal transdifferentiation untested
    • Single-study finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NUP37's core structural role in the Y-complex mechanistically connects to its diverse signaling functions (YAP-TEAD, DNMT1, PI3K/AKT) and to its stability regulation remains unresolved.
  • No unified model linking nuclear-pore function to oncogenic signaling roles
  • Direct vs nucleoporin-scaffold-mediated nature of signaling interactions undefined
  • Human structural data on the full Y-complex context for NUP37 not available in corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0005635 nuclear envelope 2
Partners
DEPDC1BDNMT1ELYSNUP160TRIM28YAP1
Complex memberships
Y-complex (nuclear pore complex)

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Crystal structure of S. pombe Nup37 in complex with Nup120 (a 174-kDa subassembly forming one short arm of the Y-complex) shows that Nup37 binds near the bend of the L-shaped Nup120 protein, potentially stabilizing the relative orientation of its two domains; reconstitution assays pinpointed residues crucial for this interaction; in vivo and in vitro results showed ELY5/ELYS binds near the Nup120-Nup37 interface; both Nup37 and ELY5 integrate directly via Nup120/160 into the heptameric Y-complex. X-ray crystallography, reconstitution assays, in vitro binding assays, cell biological experiments Proceedings of the National Academy of Sciences of the United States of America High 22955883
2017 NUP37 interacts with YAP protein and enhances the interaction between YAP and TEAD, thereby activating YAP/TEAD transcriptional signaling; knockdown of NUP37 inhibited HCC cell growth, migration, invasion, and metastasis. Co-immunoprecipitation, overexpression and knockdown experiments, cell growth/migration/invasion assays, in vivo mouse model Oncotarget Medium 29228669
2024 TRIM28 was identified as an interacting protein of NUP37 and upregulates NUP37 protein levels; TRIM28-mediated SUMOylation of NUP37 at Lys114/118/246 inhibits K27-linked polyubiquitination of NUP37, thereby blocking its proteasomal degradation and increasing NUP37 protein stability, which promotes lipid synthesis and HCC progression. Co-immunoprecipitation, western blotting, mutagenesis (SUMOylation site identification), ubiquitination assays, xenograft mouse models Oncogene Medium 39294431
2024 NUP37 interacts with DNMT1 and promotes proliferation and invasion of glioma cells through this interaction; overexpression of DNMT1 rescued the adverse effects caused by NUP37 depletion, placing NUP37 upstream of DNMT1-mediated DNA methylation in glioma. Co-immunoprecipitation, knockdown/overexpression experiments, cell proliferation and invasion assays Cell death discovery Low 39174498
2023 DEPDC1B physically binds NUP37 (verified by co-immunoprecipitation) and acts upstream of NUP37; NUP37 overexpression reversed the inhibitory effects of DEPDC1B silencing on CRC cell proliferation, migration, invasion, and PI3K/AKT signaling, placing NUP37 downstream of DEPDC1B in this pathway. Co-immunoprecipitation, siRNA knockdown, overexpression rescue, flow cytometry, western blotting, in vivo xenograft Molecular medicine reports Low 37203403
2026 ASCL1 directly binds the NUP37 promoter and suppresses NUP37 transcription; NUP37 knockdown enhanced ASCL1/miR124/p53shRNA-mediated transdifferentiation and nuclear shrinkage, while NUP37 overexpression had the opposite effect, establishing NUP37 as a regulator of nuclear pore complex abundance and nuclear size during neuronal conversion. Chromatin binding assay (ASCL1 promoter binding), knockdown and overexpression experiments, live-cell imaging of nuclear size during transdifferentiation Stem cell reports Medium 41759523

Source papers

Stage 0 corpus · 8 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Molecular basis for Nup37 and ELY5/ELYS recruitment to the nuclear pore complex. Proceedings of the National Academy of Sciences of the United States of America 62 22955883
2017 NUP37, a positive regulator of YAP/TEAD signaling, promotes the progression of hepatocellular carcinoma. Oncotarget 25 29228669
2020 NUP37 silencing induces inhibition of cell proliferation, G1 phase cell cycle arrest and apoptosis in non-small cell lung cancer cells. Pathology, research and practice 19 32014308
2021 Evaluation of Oncogene NUP37 as a Potential Novel Biomarker in Breast Cancer. Frontiers in oncology 11 34386417
2023 DEPDC1B is involved in the proliferation, metastasis, cell cycle arrest and apoptosis of colon cancer cells by regulating NUP37. Molecular medicine reports 9 37203403
2024 NUP37 accumulation mediated by TRIM28 enhances lipid synthesis to accelerate HCC progression. Oncogene 8 39294431
2024 NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation. Cell death discovery 4 39174498
2026 ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37. Stem cell reports 0 41759523

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