Affinage

ILF2

Interleukin enhancer-binding factor 2 · UniProt Q12905

Length
390 aa
Mass
43.1 kDa
Annotated
2026-06-10
82 papers in source corpus 40 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ILF2 (NF45) is a nucleic-acid-binding regulatory protein that operates principally as the obligate dimerization partner of NF90/NF110 (ILF3), forming heterodimers that act on DNA and RNA across transcription, RNA metabolism, and genome maintenance (PMID:7519613, PMID:18458058, PMID:22833610). Structurally, NF45 and its partner each contain a catalytically dead DZF (nucleotidyltransferase-like) domain that mediates dimerization, and NF45 uses the same interface to bind alternative partners such as SPNR and Zfr (PMID:22833610); NF45 acts as a conformational scaffold that substantially enhances NF90's affinity and altered binding mode for both single- and double-stranded RNA and confers RNA chaperone (annealing/strand-displacement) activity on the complex (PMID:29040738, PMID:28062840). At the chromatin level the complex serves as a sequence-specific transcriptional regulator, reconstituting NF-AT DNA-binding at the IL-2 enhancer, driving IL-13, c-fos, and immediate-early gene (EGR1, FOS, JUN) transcription, and being recruited by NFAT to the rDNA promoter to support T-cell activation (PMID:7519613, PMID:20051514, PMID:26381409, PMID:31022259, PMID:33555115). In RNA metabolism the complex is a negative regulator of miRNA biogenesis, binding pri-miRNAs (let-7a, miR-133a, miR-7) to block Microprocessor access and attenuate METTL3/14-mediated m6A modification of pri-miRNAs, with physiological consequences in muscle and hepatocellular carcinoma (PMID:19398578, PMID:25918244, PMID:27519414, PMID:41351330); it additionally functions as an IRES trans-acting factor for cIAP1 and XIAP translation, governs Alu-inverted-repeat-dependent A-to-I editing and splicing, and modulates mRNA export and stability of selected transcripts via THOC4 (PMID:19893574, PMID:23129811, PMID:40156862, PMID:33975879). ILF2 also maintains genome integrity, participating in NHEJ-mediated double-strand-break repair through the DNA-PK complex and resolving R-loops by recruiting RNA:DNA helicases, and the NF90-NF45 complex is required for proper cell division, 60S ribosomal subunit biogenesis, and suppression of a p53/p21 response (PMID:9442054, PMID:21969602, PMID:37047232, PMID:26240280, PMID:18458058). ILF2 is frequently exploited in cancer, where 1q21-amplified ILF2 promotes tolerance of genomic instability in multiple myeloma via YB-1/U2AF65 and is stabilized post-translationally by the deubiquitinase USP5 (PMID:28669490, PMID:41523258).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Established ILF2's founding identity by showing NF45 is a subunit of the NF-AT DNA-binding complex at the IL-2 enhancer, defining a transcriptional role from the outset.

    Evidence Affinity-purified His-tagged NF45/NF90 reconstituting NF-AT EMSA activity in Jurkat T-cells with immunofluorescence localization

    PMID:7519613

    Open questions at the time
    • Did not resolve which subunit confers sequence specificity
    • No structural basis for DNA binding
  2. 1998 High

    Linked NF45/NF90 to genome maintenance by showing physical and functional association with the DNA-PK (DNA-PKcs–Ku) complex, foreshadowing a DSB-repair role.

    Evidence Reciprocal co-IP, in vitro DNA-PK kinase assay using recombinant proteins, EMSA in two cell systems

    PMID:9442054 PMID:9843854

    Open questions at the time
    • Functional consequence of phosphorylation unknown at the time
    • Direct role in repair not yet demonstrated
  3. 2005 Medium

    Provided gain/loss-of-function evidence that NF45 directly activates IL-2 gene expression, moving beyond binding to causal transcriptional output.

    Evidence Stable sense/antisense NF45 expression in Jurkat with IL-2 luciferase reporter and ELISA

    PMID:15817156

    Open questions at the time
    • Large reporter effect versus modest protein change unexplained
    • Single cell line
  4. 2008 High

    Defined NF45 as a regulatory subunit reciprocally co-stabilizing NF90/NF110 at the protein level and essential for normal cell division.

    Evidence Reciprocal siRNA depletion with immunoblotting, flow cytometry, and time-lapse microscopy showing multinucleated cells

    PMID:18458058

    Open questions at the time
    • Mechanism of post-transcriptional co-stabilization not defined
    • Cause of division defect not yet traced
  5. 2009 High

    Identified the complex as a negative regulator of miRNA biogenesis acting by steric occlusion of the Microprocessor, and as an IRES trans-acting factor for cIAP1.

    Evidence Overexpression/knockdown with RIP and pri-miRNA accumulation assays; RNA affinity chromatography plus IRES translation assay

    PMID:19398578 PMID:19893574

    Open questions at the time
    • Exact structural basis of Microprocessor blocking not resolved
    • Generality across pri-miRNAs incomplete
  6. 2011 High

    Demonstrated a direct functional role in NHEJ-mediated double-strand-break repair, converting the earlier DNA-PK association into a mechanistic repair function.

    Evidence In vitro NHEJ assay with immunodepletion, γ-H2AX foci, IR sensitivity, and in vivo end-joining

    PMID:21969602

    Open questions at the time
    • Precise step in NHEJ catalysis acted upon unclear
    • Relationship to RNA-binding functions not addressed
  7. 2012 High

    Provided the structural foundation—an atomic model of the DZF dimerization interface—revealing catalytically dead nucleotidyltransferase folds and explaining partner promiscuity.

    Evidence 1.9-Å crystal structure of NF90/NF45 plus interface-mutant co-IP with SPNR and Zfr; parallel splicing-modulation and XIAP/cIAP1 ITAF studies

    PMID:22504300 PMID:22833610 PMID:23129811

    Open questions at the time
    • Structure of RNA-bound complex not solved
    • How dimer architecture dictates each downstream activity unresolved
  8. 2015 High

    Expanded the functional repertoire to ribosome biogenesis and to transcriptional coactivation of c-fos, while linking miRNA suppression to in vivo muscle phenotypes.

    Evidence Pre-60S affinity purification with RPL11 epistasis; in vitro reconstituted c-fos transcription with ChIP; NF90-NF45 transgenic mouse with pri-miR-133a binding

    PMID:25918244 PMID:26240280 PMID:26381409

    Open questions at the time
    • How one complex coordinates ribosome biogenesis with transcription unknown
    • Domain requirements differ across functions
  9. 2016 High

    Mechanistically defined how NF45 potentiates NF90, establishing the heterodimer as an RNA chaperone and enhanced RNA-binding module.

    Evidence In vitro RNA annealing/strand-displacement assays, biophysical binding comparison of monomer vs heterodimer, HCV replication and VEGF mRNA assays

    PMID:27519414 PMID:28062840 PMID:29040738

    Open questions at the time
    • Structural basis of scaffold-induced affinity change not visualized
    • Cellular targets of chaperone activity incompletely mapped
  10. 2017 High

    Connected ILF2 to cancer-associated genomic instability tolerance and to stem-cell/pluripotency gene regulation, broadening its physiological reach.

    Evidence ILF2-YB-1-U2AF65 co-IP and mRNA stability/drug-sensitivity assays in myeloma; CRISPR KO and RIP-seq in ESCs

    PMID:28487382 PMID:28669490

    Open questions at the time
    • Whether YB-1 axis is general or myeloma-specific unclear
    • Direct ILF2 RNA targets in ESCs only partially defined
  11. 2019 Medium

    Catalogued additional partner- and target-specific roles spanning transcriptional repression of PTEN, CREB/E2F1 interactions, and antiviral restriction.

    Evidence ChIP/luciferase at PTEN promoter; co-IP domain mapping for CREB and E2F1; co-IP and viral replication assays for JEV and EV71

    PMID:30881868 PMID:31212927 PMID:31423236 PMID:31878072 PMID:31908894

    Open questions at the time
    • Several interactions rest on single co-IPs without reciprocal validation
    • Direct versus complex-mediated DNA binding not always separated
  12. 2021 Medium

    Tied the complex's transcriptional activity to T-cell activation through NFAT-driven nucleolar rDNA transcription and to oncogenic mRNA export via THOC4.

    Evidence NFAT-NF45/NF90 co-IP and rDNA-promoter ChIP with mouse transplant models; ILF2-THOC4 co-IP, RIP, export and stability assays

    PMID:33555115 PMID:33975879

    Open questions at the time
    • How ARRE2-like rDNA recognition occurs structurally unknown
    • Selectivity of pluripotency-mRNA export incompletely explained
  13. 2022 Medium

    Extended ILF2's RNA-related functions to APOBEC3B deaminase modulation, pri-miRNA m6A regulation, and beta-cell metabolic compensation via p53 suppression.

    Evidence A3B interactome MS and deaminase assays; in vitro m6A modification assay; beta-cell conditional KO with dominant-negative p53 rescue

    PMID:35145187 PMID:35614067 PMID:41351330

    Open questions at the time
    • Direct vs RNA-bridged A3B interaction partly unresolved
    • Mechanism of p53 suppression in beta cells not molecularly defined
  14. 2023 Medium

    Established ILF2 as a regulator of R-loop homeostasis acting with NUSAP1 to limit DNA-damage-induced R-loop accumulation.

    Evidence AP-MS, co-IP with domain mapping, confocal colocalization, S9.6 R-loop immunostaining with NUSAP1 epistasis

    PMID:37047232

    Open questions at the time
    • Whether ILF2 acts via helicase recruitment here not yet shown
    • Single-lab functional epistasis
  15. 2025 Medium

    Refined the structural model of dsRNA recognition (oligomeric coating of long dsRNA, Alu-inverted-repeat targeting) and defined post-translational control of ILF2 stability by USP5, alongside cancer-relevant CDK4 mRNA stabilization.

    Evidence SAXS/CLMS/EM integrative modeling with Alu-IR functional annotation; USP5 co-IP, catalytic-mutant ubiquitination assay, WP1130 rescue; DYNLL1-ILF2-CDK4 mRNA RIP and stability assays

    PMID:38824222 PMID:40156862 PMID:41523258

    Open questions at the time
    • High-resolution dsRNA-bound structure still lacking
    • USP5 and DYNLL1 axes each rest on single-lab data
  16. 2026 Medium

    Showed that endogenous dsRNAs (ICAM1/ICAM1-AS) can entrap and inactivate the ILF2/ILF3 complex to repress EIF4E and global translation, revealing a sensing/sequestration mode of regulation.

    Evidence dsRNA pulldown of ILF2/ILF3, CRISPR KO vs shRNA comparison, EIF4E transcription and global protein synthesis assays

    PMID:41512856

    Open questions at the time
    • Generality of dsRNA entrapment beyond ICAM1 unknown
    • Single-lab mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold partner integrates and switches between transcription, miRNA/splicing/editing control, ribosome biogenesis, DSB repair, and R-loop resolution—and what determines target selection in each context—remains unresolved.
  • No unifying model linking distinct molecular activities
  • No high-resolution structure of nucleic-acid-bound functional states
  • Determinants of context-specific target choice unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0003723 RNA binding 5 GO:0140110 transcription regulator activity 5 GO:0045182 translation regulator activity 2 GO:0060089 molecular transducer activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005730 nucleolus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
DNA-PKCSILF3KU70KU80NUSAP1THOC4USP5YB-1
Complex memberships
DNA-PK complex (DNA-PKcs-Ku70-Ku80)NF-AT/purine-box DNA-binding complexNF110-NF45 heterodimerNF90-NF45 (ILF3-ILF2) heterodimer

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 NF45 (ILF2) and NF90 are the 45-kDa and 90-kDa subunits of the NF-AT transcription factor complex that binds the IL-2 enhancer antigen receptor response element (ARRE); affinity-purified histidine-tagged NF45 and NF90 reconstitute NF-AT DNA-binding activity that is enhanced by T-cell stimulation and blocked by cyclosporin A or FK506. Both proteins localize to the nucleus of Jurkat T-cells. Affinity purification (nickel chelate), EMSA, immunofluorescence microscopy, transient expression of tagged proteins in Jurkat T-cells The Journal of biological chemistry High 7519613
1998 NF45 and NF90 interact with the DNA-dependent protein kinase (DNA-PK) complex (DNA-PKcs and Ku subunits) and stabilize a DNA-PKcs–Ku–DNA complex; NF45 and NF90 are substrates for DNA-PK phosphorylation in vitro; recombinant NF90 promotes DNA-PKcs–Ku–DNA complex formation; antibodies to NF90 or NF45 co-immunoprecipitate DNA-PKcs. EMSA, in vitro kinase assay, co-immunoprecipitation, amino-terminal sequence analysis, immunoblotting The Journal of biological chemistry High 9442054
1998 NF45 and NF90, together with Ku70, Ku80, and DNA-PKcs, form a purine-box/NFAT DNA-binding complex in human bronchial epithelial cells; antibodies to Ku potently inhibit the purine-box DNA-binding complex. Immunohistochemistry, EMSA with blocking antibodies, co-immunoprecipitation The American journal of physiology Medium 9843854
2005 NF45 (ILF2) functions as a transcriptional activator of IL-2 gene expression; stable overexpression of NF45 sense cDNA in Jurkat T-cells increased IL-2 luciferase reporter activity ~120-fold and IL-2 protein ~2-fold; antisense suppression had the opposite effect. The human NF45 gene was mapped to chromosome 1q21.3. Stable transfection, luciferase reporter assay, ELISA, fluorescence in situ hybridization Experimental cell research Medium 15817156
2006 The DRBP76 (NF90)–NF45 heterodimer selectively forms in neuronal but not glioma cells, binds the HRV2 IRES, associates with the translation apparatus, and arrests translation at the HRV2 IRES by preventing PV-RIPO RNA assembly into polysomes. Size exclusion chromatography, ribosomal profile analysis (polysome fractionation), IRES-binding assay, cell-type specific heterokaryon analysis Journal of virology High 16809299
2008 NF45 is a regulatory subunit of NF90-NF45 and NF110-NF45 heterodimeric core complexes; depletion of NF45 by RNAi causes dramatic reduction in NF90 and NF110 protein levels (and vice versa for NF90 depletion), demonstrating post-transcriptional co-stabilization by protein–protein interaction. Depletion of NF90-NF45 (but not NF110-NF45) inhibits DNA synthesis and causes formation of giant multinucleated cells, revealing a critical role in normal cell division. RNA interference (siRNA), immunoblotting, flow cytometry, cell growth assays, time-lapse microscopy Molecular and cellular biology High 18458058
2009 The NF90–NF45 complex functions as a negative regulator of miRNA biogenesis: overexpression inhibits pri-miRNA processing to pre-miRNA, causing accumulation of pri-miRNAs; NF90-NF45 binds endogenous pri-miRNAs (higher affinity for pri-let-7a) but does not interact with the Microprocessor complex, suggesting steric blocking of Microprocessor access. Overexpression, quantitative RT-PCR, RNA immunoprecipitation, RNA polymerase II inhibition assay (alpha-amanitin), RNAi knockdown Molecular and cellular biology High 19398578
2009 NF45 is an IRES trans-acting factor (ITAF) required for cap-independent translation of cIAP1 mRNA during the unfolded protein response; NF45 binds the cIAP1 IRES (identified by RNA affinity chromatography) and enhances IRES-dependent translation of endogenous cIAP1. RNA affinity chromatography, enzymatic cleavage mapping (secondary structure), RNAi knockdown, IRES-driven translation assay Cell death and differentiation High 19893574
2010 NF45 co-localizes with IBDV viral proteins VP1, VP2, and VP3 at viral replication sites in the cytoplasm of infected cells; co-immunoprecipitation confirmed protein–protein association; siRNA-mediated NF45 knockdown increased virus yield ~5-fold, indicating NF45 restricts IBDV replication as part of a cellular defense mechanism. Immunofluorescence, co-immunoprecipitation, siRNA knockdown, viral yield assay Journal of virology Medium 20702628
2010 NF45 and NF90 bind the HS4 element in the IL-13 distal promoter and are required for HS4-dependent IL-13 transcription in T cells; binding was demonstrated by DNA affinity chromatography with mass spectrometry, ChIP, and gel shift; HS4 activity was virtually abrogated in NF45+/- primary Th2 cells. DNA affinity chromatography coupled with tandem MS, ChIP, EMSA, transient transfection of HS4-IL13 reporters in primary NF45+/- Th2 cells The Journal of biological chemistry High 20051514
2011 The NF90/NF45 complex participates in DNA double-strand break repair via non-homologous end joining (NHEJ): immunodepletion of NF90/NF45 from nuclear extracts reduced in vitro DNA end-joining activity; NF90/NF45-depleted cells accumulated γ-H2AX foci and showed increased sensitivity to ionizing radiation; in vivo end-joining was also reduced. Multinucleated phenotype upon depletion was traced to incomplete cytokinesis followed by cell fusion. In vitro NHEJ assay with immunodepletion, gamma-H2AX foci quantification, ionizing radiation sensitivity assay, time-lapse microscopy, RNAi knockdown Molecular and cellular biology High 21969602
2011 NF45 interacts with HCV core protein (HCVc174) in an RNA-dependent manner; NF45 and HCVc174 co-localize in nucleus and cytoplasm, with co-localization shifting to cytoplasm when virus replicates. Affinity purification, LC-MS/MS proteomics, pull-down, confocal imaging Journal of proteome research Low 21823664
2012 Crystal structure of the NF90/NF45 dimerization complex at 1.9-Å resolution reveals that both proteins contain a 'DZF' domain with structural similarity to template-free nucleotidyltransferases, but both have lost critical catalytic residues and are not functional enzymes; NF45 also dimerizes with SPNR and Zfr through the same NF90 binding interface, demonstrated by co-immunoprecipitation with site-specific NF90 interface mutants. X-ray crystallography (1.9-Å), co-immunoprecipitation with site-specific mutants Nucleic acids research High 22833610
2012 2'-fluoro (2'-F) modified antisense oligonucleotides form heteroduplexes that are specifically recognized by the ILF2/ILF3 (NF45/NF90) complex; recruitment of ILF2/3 to pre-mRNA near an exon causes exon skipping in cell culture and in mice, demonstrating that ILF2/3 can modulate alternative splicing. 2'-F ASO treatment, cell culture and in vivo mouse experiments, exon skipping analysis, protein recruitment assay Nature chemical biology High 22504300
2012 NF45 ITAF activity is required for IRES-mediated translation of XIAP and cIAP1 mRNAs; cells deficient in NF45 show reduced IRES-dependent translation of these targets, leading to dysregulated survivin and cyclin E expression, explaining cytokinesis impairment and senescence-like phenotype; AU-rich content (>60%) of 5' UTRs predicts NF45 dependence. RNAi knockdown, IRES reporter assays, bioinformatic analysis of 5' UTR composition, cell cycle and ploidy analysis Molecular and cellular biology Medium 23129811
2012 Depletion of NF90/NF45 in HPV-transformed cervical carcinoma cells restores p53 and p21 protein expression; p53 is regulated post-transcriptionally (mRNA level unchanged), while p21 induction is p53-dependent at the transcriptional level; NF90 depletion attenuates HPV E6 RNA expression by inhibiting transcription from the HPV early promoter, thereby de-repressing the E6/E6AP-mediated p53 degradation pathway. RNAi knockdown, immunoblotting, qRT-PCR, p53 RNAi epistasis, PARP cleavage assay, camptothecin sensitivity assay Oncogene Medium 23208500
2015 The NF45/NF90 heterodimer associates with precursors to 60S ribosomal subunits (pre-60S particles) in nucleoli; association requires the dsRNA-binding domains of NF90; depletion of NF45 and NF90 causes a 60S biogenesis defect, alters nucleolar morphology to a characteristic spherical shape, and triggers a p53/p21 response dependent on RPL11. Tandem affinity purification, density gradient sedimentation, RNAi knockdown, nucleolar morphology analysis, RPL11 epistasis (double knockdown), rRNA processing assay Molecular and cellular biology High 26240280
2015 NF45-NF90 and NF45-NF110 complexes function as transcriptional coactivators of the c-fos gene: purified complexes stimulate c-fos transcription in a defined in vitro system via both the upstream enhancer and core promoter; coactivation does not require dsRNA binding domains; the complexes cooperate with PC4 and Mediator; ChIP shows dynamic occupancy at the c-fos enhancer/promoter before and after serum induction. In vitro transcription reconstitution with purified components, ChIP, RNAi knockdown in mouse cells, domain-deletion mutants The Journal of biological chemistry High 26381409
2015 Overexpression of NF90-NF45 in transgenic mice suppresses myogenic miRNA biogenesis (including miR-133a) by binding pri-miR-133a-1 and inhibiting its processing, resulting in elevated dynamin 2 expression, skeletal muscle atrophy, and centronuclear muscle fibers in vivo. NF90-NF45 double-transgenic mouse model, miRNA microarray, qRT-PCR, in vitro pri-miRNA binding assay, histological analysis Molecular and cellular biology High 25918244
2016 NF90-NF45 negatively regulates miR-7 biogenesis in hepatocellular carcinoma by binding pri-miR-7-1 in vitro, blocking its processing; NF90/NF45 depletion elevates mature miR-7, decreases EGFR levels, reduces AKT phosphorylation, and inhibits HCC cell proliferation. miRNA microarray, qRT-PCR, RNAi knockdown, in vitro pri-miRNA binding assay, overexpression, immunoblotting The Journal of biological chemistry High 27519414
2016 NF90 (DRBP76) has selective RNA chaperone activity (RNA annealing and strand displacement) that is substantially enhanced by heterodimer formation with NF45; NF45 acts as a conformational scaffold improving NF90 'matchmaking' of complementary ssRNAs; the NF90-NF45 complex stimulates the first step of HCV RNA replication in vitro and stabilizes a regulatory element in VEGF mRNA by protein-guided RNA structural changes. In vitro RNA chaperone assays (annealing, strand displacement), biophysical binding analysis, HCV replication assay in vitro, VEGF mRNA structural analysis Nucleic acids research High 29040738
2016 Complex formation of NF90 with NF45 substantially improves NF90 RNA-binding capacity, modifies binding mode, enhances affinity for both ss- and dsRNA, and provides thermodynamic stabilization; NF45 is proposed to act as a conformational scaffold altering the cooperative interplay of NF90's RNA-binding motifs. Biophysical analysis (purified recombinant proteins), biochemical RNA-binding assays comparing monomer vs. heterodimer The Biochemical journal High 28062840
2017 Elevated ILF2 expression (driven by 1q21 amplification) promotes tolerance of genomic instability and resistance to DNA-damaging agents in multiple myeloma by modulating YB-1 nuclear localization and its interaction with splicing factor U2AF65, which promotes mRNA processing and stabilization of transcripts involved in homologous recombination. siRNA knockdown, overexpression, co-immunoprecipitation (ILF2-YB-1 and YB-1-U2AF65), mRNA stability assay, drug sensitivity assay, in vivo xenograft Cancer cell High 28669490
2017 NF45 and NF90/NF110 regulate embryonic stem cell pluripotency and differentiation; loss of NF45 or NF90+NF110 impairs ESC proliferation and causes dysregulated differentiation; NF45 and NF90/NF110 physically interact and influence each other's expression; NF90/NF110 RIP-seq identified direct target mRNAs involved in proliferation and RNA processing. RNAi screen, CRISPR KO, RNA immunoprecipitation followed by sequencing (RIP-seq), transcriptome analysis, proliferation assays RNA (New York, N.Y.) High 28487382
2019 NF45 and NF90/NF110 pre-occupy the promoters of immediate early genes (EGR1, FOS, JUN) constitutively; cellular stimulation with PMA increases NF90/NF110 chromatin association while decreasing NF45 association at these promoters; knockdown of either NF90/NF110 or NF45 attenuates inducible expression of EGR1, FOS, and JUN. ChIP, inducible shRNA knockdown, qRT-PCR, immunoblotting PloS one Medium 31022259
2019 ILF2 functions as a transcription factor that directly binds the upstream regulatory region of PTEN and suppresses its expression; ChIP and luciferase reporter assays demonstrated direct binding; this enables anchorage-independent survival of NSCLC cells. ChIP, luciferase reporter assay, cell adhesion and apoptosis assays in suspension culture Oncology letters Medium 31423236
2019 ILF2 directly binds CREB protein via the pKID domain of CREB; ILF2 stabilizes CREB at the protein level (not mRNA level) and promotes CREB phosphorylation at Ser133; this interaction promotes malignant phenotypes of liver cancer cells. Co-immunoprecipitation, immunoblotting, domain mapping, protein stability assays Analytical cellular pathology (Amsterdam) Low 30881868
2019 ILF2 interacts with E2F1 in small cell lung cancer cells; ILF2 maintains mitochondrial quality and promotes oxidative phosphorylation; suppression of E2F1 reverses ILF2-induced tumor growth and mitochondrial function enhancement. Co-immunoprecipitation, RNA-seq, dual luciferase reporter assay, mitochondrial membrane potential assay, oxygen consumption rate measurement, xenograft models Cancer biology & medicine Medium 31908894
2019 ILF2 inhibits Japanese encephalitis virus (JEV) replication: ILF2 interacts with JEV NS3 protein (identified by co-IP and LC-MS/MS); ILF2 knockdown increases JEV propagation, and ILF2 overexpression reduces JEV genome synthesis; ILF2 is decreased in JEV-infected cells. Co-immunoprecipitation, LC-MS/MS, shRNA knockdown, overexpression, JEV replicon assay Viruses Medium 31212927
2019 EV71 nonstructural protein 2B interacts with ILF2 and promotes ILF2 translocation from nucleus to cytoplasm, thereby antagonizing ILF2's antiviral effects; ILF2 overexpression reduces EV71 TCID50 and plaque formation. Co-immunoprecipitation, subcellular fractionation/immunofluorescence, viral titer assay (TCID50 and PFU), microarray, siRNA knockdown Viruses Medium 31878072
2021 Upon T-cell activation, NFAT translocates to the nucleolus and interacts with the NF45/NF90 complex to promote rDNA transcription; NF45/NF90 directly binds ARRE2-like sequences in the rDNA promoter; elevated pre-rRNA is required for T-cell activation and can be suppressed by CX5461 (rDNA transcription inhibitor) to prevent allograft rejection. Co-immunoprecipitation (NFAT-NF45/NF90), ChIP (NF45/NF90 at rDNA promoter), pre-rRNA quantification, mouse transplantation models, pharmacological inhibition EMBO molecular medicine High 33555115
2021 ILF2 binds THO complex protein THOC4 as a regulatory cofactor, interacts selectively with pluripotency factor mRNAs (SOX2, NANOG, SALL4), promotes their nuclear export through assembly into export-competent mRNP complexes, and inhibits hMTR4-mediated exosomal degradation to stabilize these transcripts; nicotine induces ILF2 via JAK2/STAT3 signaling. Co-immunoprecipitation (ILF2-THOC4), RIP, RNA stability assays, mRNA nuclear export assay, ILF2 depletion in vitro and in vivo xenograft Cancer research Medium 33975879
2022 ILF2 enhances the DNA cytosine deaminase activity of APOBEC3B by ~30% when overexpressed, and ILF2 knockdown suppresses A3B deaminase activity by ~30%; ILF2 interacts with A3B in high-molecular-mass complexes identified by mass spectrometry; most interactions are RNA-dependent except for SAFB. Mass spectrometry (A3B interactome), density gradient sedimentation, deaminase activity assay, siRNA knockdown, overexpression Scientific reports Medium 35145187
2022 NF90-NF45 acts as a negative regulator of m6A modification of pri-miRNAs: NF90-NF45 attenuates METTL3/14-mediated m6A modification of pri-mir-7-1 in vitro (but not pri-mir-200a, which has lower NF90 binding affinity), thereby suppressing miR-7 biogenesis; NF90-NF45 does not interact with METTL3/14 (negative finding). In vitro m6A modification assay, overexpression, miRNA biogenesis assay, immunoprecipitation (NF90-METTL3/14 interaction—negative result) FEBS open bio Medium 41351330
2022 NF90-NF45 is essential for beta-cell compensation under high-fat diet metabolic stress; beta-cell-specific NF90-NF45-deficient mice develop hyperglycemia and decreased islet mass; NF90-NF45 suppresses p53 signaling pathway in beta cells, and a dominant-negative p53 rescues the growth retardation in NF90-NF45-depleted beta cells. Beta-cell-specific conditional knockout mice, microarray, p53-responsive luciferase reporter, dominant-negative p53 rescue, cell growth assay Scientific reports High 35614067
2023 NUSAP1 interacts with ILF2 (verified by co-immunoprecipitation and confocal colocalization) through its microtubule and charged helical domains; depletion of ILF2 alone increases camptothecin-induced R-loop accumulation and DNA damage; NUSAP1 depletion abolishes this effect, placing ILF2 as a regulator of R-loop homeostasis in response to DNA damage. Affinity purification-mass spectrometry, co-immunoprecipitation, confocal microscopy, ILF2 depletion, R-loop immunostaining (S9.6 antibody), domain truncation mapping International journal of molecular sciences Medium 37047232
2024 DYNLL1 interacts with ILF2 and facilitates ILF2 expression; ILF2 in turn interacts with CDK4 mRNA and delays its degradation, activating G1/S cell cycle progression and downstream CDK4 targets to promote HCC development. Co-immunoprecipitation, mass spectrometry, RNA sequencing, mRNA stability assay (RIP for CDK4 mRNA), xenograft and orthotopic mouse models British journal of cancer Medium 38824222
2025 USP5 is a deubiquitinase that stabilizes ILF2 by removing ubiquitin modifications; co-IP and MS identified the USP5-ILF2 interaction; catalytically inactive USP5 failed to reduce ILF2 ubiquitination, demonstrating the requirement for USP5 catalytic activity; USP5 inhibitor WP1130 downregulates ILF2 and inhibits CRC cell growth, reversed by ILF2 overexpression. Co-immunoprecipitation, LC-MS/MS, ubiquitination assay, catalytic mutant USP5, pharmacological inhibition (WP1130), xenograft mouse model American journal of cancer research Medium 41523258
2025 Integrative structural analysis of NF45-NF90 using SAXS, quantitative cross-linking mass spectrometry, machine learning, and negative-stain EM reveals architectural rearrangements upon dsRNA binding; NF45-NF90 complexes can oligomerize to coat long dsRNA stretches (>50 bp); in human cells, NF45-NF90 primarily interacts with Alu inverted repeats (AluIRs) in introns, regulating adenosine-to-inosine editing, cassette exon and back splicing, and splicing fidelity. Small angle X-ray scattering (SAXS), quantitative cross-linking mass spectrometry, machine learning structural modeling, negative stain electron microscopy, phylogenetic analysis Nucleic acids research High 40156862
2026 ICAM1 mRNA and its cis-antisense transcript ICAM1-AS form a dsRNA that entraps the ILF2/ILF3 complex, inhibiting its DNA binding in a length-dependent manner; this suppresses EIF4E transcription and global protein synthesis; the mechanism is independent of ICAM1 protein coding function. CRISPR-Cas9 protein knockout vs. shRNA knockdown comparison, overexpression of mutated ICAM1 mRNA and CDS, dsRNA pulldown of ILF2/ILF3, EIF4E transcription assay, global protein synthesis measurement Molecular cell Medium 41512856
2025 ILF2 orchestrates transcriptional and RNA splicing programs in kidney medullary epithelial cells; ILF2 knockdown disrupts gene expression and splicing programs linked to cell proliferation, cytoskeletal organization, and stress adaptation; ILF2-deficient cells show reduced proliferation, impaired nuclear integrity, and increased sensitivity to hyperosmotic stress; ILF2 expression increases during tubular repair after ischemia-reperfusion injury in mice. Single-nucleus RNA-seq, single-cell CRISPR interference screening (Perturb-seq), bulk RNA-seq, splicing analysis, hyperosmotic stress assay, mouse IRI model bioRxivpreprint Medium
2025 ILF2 orchestrates recruitment of RNA:DNA helicases to resolve R-loops; pharmacological disruption of the ILF2 complex with compound NYH0002 inhibits RNA:DNA helicase activity, elicits genome-wide DNA breaks, and induces lethality selectively in homologous recombination-deficient cancers; tumors with elevated cyclin E and E2F1 are sensitive to NYH0002. Direct binding assay (NYH0002 to ILF2 complex), helicase activity assay, genome-wide DNA damage assay, HR-deficient cancer cell lines, in vivo tumor models bioRxivpreprint Medium

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90. The Journal of biological chemistry 157 7519613
2009 The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway. Molecular and cellular biology 151 19398578
2017 ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma. Cancer cell 136 28669490
2018 Long non-coding RNA DANCR stabilizes HIF-1α and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma. Theranostics 112 30555573
1998 DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45. The Journal of biological chemistry 112 9442054
2008 Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control. Molecular and cellular biology 99 18458058
2006 The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site. Journal of virology 93 16809299
2012 Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing. Nature chemical biology 89 22504300
2005 NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function. Experimental cell research 72 15817156
2020 Circular RNA 406961 interacts with ILF2 to regulate PM2.5-induced inflammatory responses in human bronchial epithelial cells via activation of STAT3/JNK pathways. Environment international 63 32388272
2011 The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining. Molecular and cellular biology 59 21969602
2016 Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma. The Journal of biological chemistry 58 27519414
2017 The long noncoding RNA LINC00473, a target of microRNA 34a, promotes tumorigenesis by inhibiting ILF2 degradation in cervical cancer. American journal of cancer research 56 29218240
2012 NF45 dimerizes with NF90, Zfr and SPNR via a conserved domain that has a nucleotidyltransferase fold. Nucleic acids research 54 22833610
2012 Induction of p53, p21 and apoptosis by silencing the NF90/NF45 complex in human papilloma virus-transformed cervical carcinoma cells. Oncogene 54 23208500
2010 NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells. The Journal of biological chemistry 54 20051514
2024 Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target. Cell proliferation 47 38943472
2009 NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1 during the unfolded protein response. Cell death and differentiation 47 19893574
2022 LncRNA ELF3-AS1 inhibits gastric cancer by forming a negative feedback loop with SNAI2 and regulates ELF3 mRNA stability via interacting with ILF2/ILF3 complex. Journal of experimental & clinical cancer research : CR 46 36457025
2020 lncRNA AK085865 Promotes Macrophage M2 Polarization in CVB3-Induced VM by Regulating ILF2-ILF3 Complex-Mediated miRNA-192 Biogenesis. Molecular therapy. Nucleic acids 43 32668391
2010 Nuclear factor NF45 interacts with viral proteins of infectious bursal disease virus and inhibits viral replication. Journal of virology 40 20702628
2011 Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting partners of the mature hepatitis C virus core protein. Journal of proteome research 39 21823664
2017 MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma. International journal of molecular medicine 36 28259961
2014 Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC). Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 34 25286760
2015 The NF45/NF90 Heterodimer Contributes to the Biogenesis of 60S Ribosomal Subunits and Influences Nucleolar Morphology. Molecular and cellular biology 33 26240280
2021 Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer. Cancer research 29 33975879
2015 The RNA binding complexes NF45-NF90 and NF45-NF110 associate dynamically with the c-fos gene and function as transcriptional coactivators. The Journal of biological chemistry 26 26381409
2014 Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 25023405
2024 LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis. Journal of experimental & clinical cancer research : CR 24 38238853
2019 ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression. Cancer biology & medicine 24 31908894
2015 Overexpression of NF90-NF45 Represses Myogenic MicroRNA Biogenesis, Resulting in Development of Skeletal Muscle Atrophy and Centronuclear Muscle Fibers. Molecular and cellular biology 24 25918244
1998 CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku. The American journal of physiology 24 9843854
2022 ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis. Frontiers in genetics 23 35586566
2012 Nucleotide composition of cellular internal ribosome entry sites defines dependence on NF45 and predicts a posttranscriptional mitotic regulon. Molecular and cellular biology 23 23129811
2017 NF45 and NF90/NF110 coordinately regulate ESC pluripotency and differentiation. RNA (New York, N.Y.) 22 28487382
2023 NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer. International journal of molecular sciences 21 37047232
2017 NF90-NF45 is a selective RNA chaperone that rearranges viral and cellular riboswitches: biochemical analysis of a virus host factor activity. Nucleic acids research 21 29040738
2002 Ilf2 is regulated during meiosis and associated to transcriptionally active chromatin. Mechanisms of development 21 11804788
2022 LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex. Cell cycle (Georgetown, Tex.) 20 35188449
2023 Circ-ILF2 in oral squamous cell carcinoma promotes cisplatin resistance and induces M2 polarization of macrophages. Journal of cellular and molecular medicine 19 37864310
2019 ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells. Analytical cellular pathology (Amsterdam) 19 30881868
2017 Expression and Clinical Significance of ILF2 in Gastric Cancer. Disease markers 19 28831206
2023 LncRNA H19 Regulates Breast Cancer DNA Damage Response and Sensitivity to PARP Inhibitors via Binding to ILF2. International journal of molecular sciences 18 37298108
2022 Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2). Bioengineered 18 35333683
2019 LncRNA LINC00470 promotes proliferation through association with NF45/NF90 complex in hepatocellular carcinoma. Human cell 18 31612313
2019 Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3. PloS one 17 31022259
2018 ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease. Scientific reports 15 29556082
2016 The properties of the RNA-binding protein NF90 are considerably modulated by complex formation with NF45. The Biochemical journal 15 28062840
1996 Mapping interleukin enhancer binding factor 2 gene (ILF2) to human chromosome 1 (1q11-qter and 1p11-p12) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 15 8974006
2006 Molecular cloning, characterization and expression analysis of grass carp (Ctenopharyngodon idellus) NF45 (ILF2) cDNA, a subunit of the nuclear factor of activated T-cells (NF-AT). Fish & shellfish immunology 14 16533607
2010 Cloning, characterization, and expression analysis of orange-spotted grouper (Epinephelus coioides) ILF2 gene (EcILF2). Fish & shellfish immunology 13 21109006
2007 NF45 and NF90 in murine seminiferous epithelium: potential role in SP-10 gene transcription. Journal of andrology 13 17942973
2021 Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma. Frontiers in molecular biosciences 12 34568427
2024 DYNLL1 accelerates cell cycle via ILF2/CDK4 axis to promote hepatocellular carcinoma development and palbociclib sensitivity. British journal of cancer 11 38824222
2021 NF45/NF90-mediated rDNA transcription provides a novel target for immunosuppressant development. EMBO molecular medicine 11 33555115
2021 Genomic Mapping of Splicing-Related Genes Identify Amplifications in LSM1, CLNS1A, and ILF2 in Luminal Breast Cancer. Cancers 11 34439272
2021 LncRNA NR038975, A Serum-Based Biomarker, Promotes Gastric Tumorigenesis by Interacting With NF90/NF45 Complex. Frontiers in oncology 11 34900675
2015 NF45 inhibits cardiomyocyte apoptosis following myocardial ischemia-reperfusion injury. Pathology, research and practice 11 26573128
2006 Molecular cloning, characterization and expression analysis of an ILF2 homologue from Tetraodon nigroviridis. Journal of biochemistry and molecular biology 11 17129403
2018 NF45 promotes esophageal squamous carcinoma cell invasion by increasing Rac1 activity through 14-3-3ε protein. Archives of biochemistry and biophysics 10 30550728
2025 The highly conserved PIWI-interacting RNA CRAPIR antagonizes PA2G4-mediated NF110-NF45 disassembly to promote heart regeneration in mice. Nature cardiovascular research 9 39814981
2024 Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer. BMC cancer 9 38622522
2024 ILF2: a multifaceted regulator in malignant tumors and its prospects as a biomarker and therapeutic target. Frontiers in oncology 9 39735599
2019 Cellular Interleukin Enhancer-Binding Factor 2, ILF2, Inhibits Japanese Encephalitis Virus Replication In Vitro. Viruses 9 31212927
2019 ILF2 promotes anchorage independence through direct regulation of PTEN. Oncology letters 9 31423236
2022 ILF2 enhances the DNA cytosine deaminase activity of tumor mutator APOBEC3B in multiple myeloma cells. Scientific reports 8 35145187
2020 Deletion of interleukin enhancer binding factor 2 (ILF2) resulted in defective biliary development and bile flow blockage. Journal of pediatric surgery 8 32709532
2020 Interleukin-2 enhancer binding factor 2 (ILF2) in pacific white shrimp (Litopenaeus vannamei): Alternatively spliced isoforms with different responses in the immune defenses against vibrio infection. Developmental and comparative immunology 8 33383068
2019 Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects. Viruses 7 31878072
2015 Up-regulation of NF45 correlates with Schwann cell proliferation after sciatic nerve crush. Journal of molecular neuroscience : MN 7 25566957
2025 Integrative structural analysis of NF45-NF90 heterodimers reveals architectural rearrangements and oligomerization on binding dsRNA. Nucleic acids research 4 40156862
2025 lncDDR suppresses drug resistance by regulating DNA damage repair through ILF2-YB1 in T-cell acute lymphoblastic leukemia. Cancer letters 3 41412212
2026 ICAM1 mRNA entraps ILF2/ILF3 to inhibit transcription of EIF4E and global protein synthesis. Molecular cell 2 41512856
2024 Enhancing diabetic foot ulcer healing: Impact of the regulation of the FUS and ILF2 RNA‑binding proteins through negative pressure wound therapy. International journal of molecular medicine 2 39301661
2025 Mallard ILF2 negatively regulates type I IFN production through autophagy-lysosome-dependent degradation of IRF7. Journal of immunology (Baltimore, Md. : 1950) 1 40447123
2022 NF90-NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway. Scientific reports 1 35614067
2026 ILF2 cooperates with ILF3/KLF16 to drive colorectal cancer progression via modulating the behaviors of both tumor cells and M2 macrophages. Apoptosis : an international journal on programmed cell death 0 41572068
2025 [Retracted] MicroRNA‑7 functions as a tumor‑suppressor gene by regulating ILF2 in pancreatic carcinoma. International journal of molecular medicine 0 40342100
2025 Domain associated with zinc fingers-containing NF90-NF45 complex inhibits m6A modification of primary microRNA by suppressing METTL3/14 activity. FEBS open bio 0 41351330
2025 USP5-mediated stabilization of ILF2 via deubiquitination drives the tumor growth of colorectal cancer. American journal of cancer research 0 41523258
2024 ILF2 protein is a promising serum biomarker for early detection of gastric cancer. BMC cancer 0 39587551
2023 Erratum: Long non-coding RNA DANCR stabilizes HIF-1α and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma: Erratum. Theranostics 0 37908717

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