Affinage

CNBP

CCHC-type zinc finger nucleic acid binding protein · UniProt P62633

Length
177 aa
Mass
19.5 kDa
Annotated
2026-06-09
69 papers in source corpus 28 papers cited in narrative 28 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

CNBP (ZNF9) is a conserved single-stranded nucleic acid-binding protein that operates as both a transcriptional and post-transcriptional regulator of gene expression, with roles spanning vertebrate head/neural crest development, innate immunity, and intracellular mRNA logistics (PMID:12588852, PMID:28168305). Its biochemical core is a multi-zinc-knuckle, RGG-box architecture: it binds G-rich single-stranded RNA and DNA sequence-specifically (PMID:7788528), and the RGG box is essential for RNA binding and nucleic acid chaperone activity while removal converts it to a dominant negative in vivo (PMID:18703071). At the transcriptional level CNBP recognizes G-quadruplex-forming promoter elements and acts as a G4-unfolding/remodeling factor, controlling transcription of c-MYC (via a CNBP/NM23-H2 complex at NHE III1) (PMID:23774591), KRAS and NOGGIN (PMID:31219592), TCOF1 (PMID:38553547), and developmental genes including tbx2b, smarca5, wnt5b and Wnt-pathway components (PMID:23667590, PMID:25151948). Post-transcriptionally, CNBP activates cap-independent (IRES-mediated) translation by associating with translating ribosomes and forming a holo-ITAF complex with PCBP2 on the ODC mRNA IRES (PMID:17327219, PMID:20174632), drives an ODC/polyamine translational axis (PMID:34517941), stabilizes CCND1 mRNA in cooperation with lncRNA LAST (PMID:29199958), remodels lncRNA 3-D structure such as Braveheart (PMID:31919376), and forms a motor-adaptor complex with the KIF1C kinesin to traffic 3'UTR GA-rich mRNAs to cell protrusions for migration (PMID:39982819). In innate immunity CNBP is a cytosolic factor that, upon phosphorylation-induced dimerization and nuclear translocation, drives transcription of inflammatory cytokines including IL-6 and supports c-Rel-dependent IL-12β expression (PMID:28168305, PMID:30442645). Its activity is gated by regulated nuclear import via KPNB1 and by pAMPK-dependent phosphorylation that controls CNBP protein stability (PMID:37186134, PMID:39807631). Loss of one Znf9 allele in mice produces a myotonic dystrophy-like phenotype with reduced chloride channel Clc1 expression, and CNBP-dependent IRES/polyamine activity is impaired in DM2 patient cells (PMID:17335846, PMID:20174632, PMID:34517941).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 Medium

    Established the fundamental biochemical activity of CNBP: that it is a sequence-specific single-stranded nucleic acid binding protein, defining the molecular basis for all later regulatory roles.

    Evidence In vitro binding assay with recombinant GST-CNBP on G-rich ssRNA/ssDNA

    PMID:7788528

    Open questions at the time
    • Single in vitro method, no cellular targets identified
    • Did not distinguish DNA vs RNA functional preference
    • No structural determinant of specificity defined
  2. 1998 Medium

    First placed CNBP on a specific mRNA element (ribosomal protein 5'UTRs) and showed it acts as a multimer with ancillary factors, hinting at a translational regulatory function.

    Evidence In vitro RNA-protein binding and 5'UTR mutational analysis; competition with La and dependence on Ro60

    PMID:9710533

    Open questions at the time
    • Functional translational consequence not demonstrated in this study
    • Ro60 dependence mechanism unresolved
    • In vitro only
  3. 2003 High

    Connected CNBP to a defined developmental program and a transcriptional target, showing it drives proliferation and Myc expression and is required for forebrain/rostral head formation.

    Evidence Mouse Cnbp knockout with transgenic rescue, c-myc promoter CAT/reporter assays, overexpression proliferation assays; plus reporter studies of TOP/IRES translational activation

    PMID:12432575 PMID:12588852

    Open questions at the time
    • Whether Myc regulation is transcriptional, translational or both not fully separated
    • Direct promoter binding not shown in knockout study
    • Mechanism of TOP/IRES activation not molecularly defined
  4. 2006 Medium

    Refined CNBP's developmental role by placing it upstream of specific forebrain transcription factors in a pathway parallel to Otx2.

    Evidence RNAi silencing and retroviral misexpression in chick embryos with in situ readouts of BF-1, Six3, Hesx1

    PMID:16626683

    Open questions at the time
    • Direct vs indirect regulation of these TFs unresolved
    • No biochemical promoter binding shown
    • Molecular activity (transcription vs translation) not distinguished
  5. 2007 High

    Resolved how CNBP supports proliferation in vivo and defined a concrete translational mechanism, showing it forms a holo-ITAF with PCBP2 on the ODC IRES and controls neural crest cell number rather than fate.

    Evidence Proteomics/Co-IP identifying PCBP2, IRES translation assays; zebrafish morpholino knockdown with proliferation/death readouts

    PMID:17327219 PMID:17471504

    Open questions at the time
    • Stoichiometry of the CNBP-PCBP2 ITAF complex not defined
    • Generalizability beyond ODC IRES not established here
    • Link between IRES activity and proliferation phenotype indirect
  6. 2007 High

    Established the disease relevance of CNBP dosage, showing Znf9 haploinsufficiency produces a myotonic dystrophy-like phenotype tied to reduced Clc1 chloride channel expression.

    Evidence Znf9+/- mice with EMG/ECG/histology and transgenic rescue, Clc1 Western blot

    PMID:17335846

    Open questions at the time
    • Mechanism linking CNBP to Clc1 expression not defined
    • Whether effect is transcriptional or post-transcriptional unclear
    • Does not address DM2 repeat-expansion sequestration models directly
  7. 2008 High

    Mapped the structural determinants of CNBP function, demonstrating the RGG box is essential for RNA binding and chaperone activity and that domain-deletion mutants act as dominant negatives in vivo.

    Evidence Site-directed mutagenesis with in vitro biochemical assays and gain/loss-of-function in Xenopus neural crest

    PMID:18703071

    Open questions at the time
    • High-resolution structure of nucleic-acid-bound CNBP absent
    • Individual zinc-knuckle contributions only partially resolved
    • Chaperone mechanism not visualized
  8. 2010 High

    Linked the IRES-translation mechanism directly to disease, showing CNBP associates with translating ribosomes and binds the ODC IRES, with reduced activity in DM2 patient myoblasts.

    Evidence Polysome profiling, ribosome isolation, direct RNA binding, IRES translation assay in primary human myoblasts

    PMID:20174632

    Open questions at the time
    • Cause of reduced activity in DM2 cells (protein level vs sequestration) not pinpointed here
    • Full set of CNBP-dependent IRES mRNAs not enumerated
    • Ribosome association mechanism undefined
  9. 2012 Medium

    Placed CNBP in stress-responsive mRNA handling by showing it associates with poly(A) binding protein and accumulates in stress granules, with conserved behavior of the yeast ortholog Gis2.

    Evidence Co-IP, fluorescence localization, and polysome/stress-granule fractionation in human cells plus yeast ortholog analysis

    PMID:23285195

    Open questions at the time
    • Functional consequence of stress-granule localization not established
    • Human CNBP role partly inferred from yeast Gis2
    • Direct vs RNA-bridged PABP interaction not fully resolved
  10. 2013 High

    Defined CNBP's signature transcriptional mechanism — binding G-rich promoter sequences and modulating G-quadruplex structures — and identified protein partners and direct developmental targets.

    Evidence EMSA/CD/FRET/ChIP/SPR/Co-IP at the c-myc NHE III1 with NM23-H2; yeast one-hybrid, EMSA, ChIP and zebrafish loss-of-function for tbx2b/smarca5/wnt5b; biophysics of CNBP dimerization and ssNA-induced stabilization; Drosophila IRES-dependent dMyc translation control

    PMID:23667590 PMID:23774591 PMID:24161561 PMID:24275942

    Open questions at the time
    • Whether CNBP folds or unfolds G4 at c-myc not fully reconciled across targets
    • Role of NM23-H2 partnership generality unknown
    • Coordination of dual transcriptional/translational Myc control unclear
  11. 2014 Medium

    Extended CNBP's transcriptional reach into Wnt signaling, showing dose-dependent regulation of Wnt pathway components that feed back onto c-myc/ccnd1/axin2.

    Evidence Zebrafish loss-of-function with RT-PCR of cdk14, ptk7, tcf7l2, wnt5

    PMID:25151948

    Open questions at the time
    • Direct promoter binding for all targets not shown
    • Dose-dependence mechanism unexplained
    • Downstream phenotypic consequence not quantified
  12. 2017 High

    Established CNBP as a regulated innate-immune transcription factor and an mRNA-stabilizing factor, showing inducible nuclear translocation driving inflammatory cytokine transcription and lncRNA-assisted CCND1 mRNA stabilization.

    Evidence ChIP, dual-luciferase, phosphorylation-dependent nuclear translocation, zebrafish Shigella infection for IL-6 axis; RIP-seq/RNA-seq and stability assays for the CNBP-LAST-CCND1 axis

    PMID:28168305 PMID:29199958

    Open questions at the time
    • Identity of the kinase driving CNBP dimerization not defined here
    • Full inflammatory target set incomplete
    • Mechanism of LAST-CNBP cooperativity at the molecular level unresolved
  13. 2018 High

    Defined a specific innate-immune signaling mechanism in macrophages, showing cytosol-to-nucleus translocation of CNBP is required for c-Rel activation and Th1-polarizing IL-12β expression independent of canonical NF-κB.

    Evidence Cnbp knockout mice, nuclear translocation and c-Rel DNA-binding assays, Toxoplasma infection and cytokine measurements

    PMID:30442645

    Open questions at the time
    • Direct vs indirect CNBP-c-Rel interaction not fully defined
    • Signal/kinase triggering translocation not identified
    • Relationship to G4/transcriptional mechanism unclear
  14. 2019 High

    Resolved the directionality of CNBP's G-quadruplex action, demonstrating it unfolds G4 structures to relieve transcriptional silencing of oncogene promoters.

    Evidence In vitro G4-unfolding assays, cellular CNBP depletion with RT-qPCR (KRAS), and zebrafish in vivo NOG repression

    PMID:31219592

    Open questions at the time
    • Reconciliation with G4-promoting activity at c-myc not addressed
    • Genome-wide G4 targets not mapped
    • Kinetics of unfolding in vivo unknown
  15. 2020 High

    Demonstrated CNBP's RNA chaperone activity on a functional lncRNA, showing it remodels the 3-D structure of Braveheart via a defined RNA motif.

    Evidence SAXS and structural ensemble analysis of Bvht with and without CNBP

    PMID:31919376

    Open questions at the time
    • Functional/cellular consequence of remodeling not tested here
    • Atomic-resolution structure of complex absent
    • Which CNBP domains contact the RHT/AGIL motif not mapped
  16. 2021 High

    Connected CNBP's ODC IRES-translation activity to a physiological polyamine axis with disease relevance and extended its G4-unfolding role to a viral RNA genome.

    Evidence Drosophila muscle knockdown with dOdc/polyamine measurements, rescue, and DM2 patient muscle analysis; in vitro G4-unfolding of SARS-CoV-2 +/- strand RNA

    PMID:33807682 PMID:34517941

    Open questions at the time
    • Mammalian counterpart of the polyamine axis not directly tested
    • In vivo antiviral consequence of G4 unfolding not established in these studies
    • Selectivity among many cellular G4 substrates unclear
  17. 2022 Medium

    Proposed a dual antiviral mechanism in which CNBP both activates IFNβ transcription upon RNA sensing and directly competes with viral N protein to block phase separation of SARS-CoV-2 RNA.

    Evidence (preprint) CNBP-deficient mice with viral loads, direct RNA binding, LLPS competition, IFNβ transcription assays

    PMID:35547851

    Open questions at the time
    • Preprint, not peer-reviewed
    • Relative contribution of IFNβ vs LLPS mechanisms not quantified
    • Phosphorylation trigger for translocation not identified
  18. 2023 Medium

    Identified the nuclear import machinery and a phase-separation-based mechanism by which CNBP regulates SWI/SNF activity and ribosome biogenesis.

    Evidence Co-IP/MS identifying KPNB1, ChIP, reporter assays, and cell-penetrating peptide disruption of CNBP condensates in neuroblastoma cells

    PMID:37186134

    Open questions at the time
    • Direct CNBP-SMARCC2 interaction interface not mapped
    • Physiological conditions inducing CNBP condensation unclear
    • Single-lab condensate model
  19. 2024 High

    Added TCOF1 as a G-quadruplex-regulated CNBP target, showing high-affinity binding to both folded and unfolded promoter PQS and bidirectional transcriptional modulation.

    Evidence CD, fluorescence binding with Kd, ChIP in HeLa, luciferase reporter, and zebrafish overexpression/knockdown of nolc1

    PMID:38553547

    Open questions at the time
    • Why both overexpression and knockdown raise nolc1 not mechanistically resolved
    • In vivo G4 folding state at the TCOF1 promoter unknown
    • Cofactors at this promoter not identified
  20. 2025 High

    Revealed a cytoskeletal trafficking role, defining CNBP as a kinesin adaptor that links GA-rich 3'UTR mRNAs to KIF1C for microtubule transport supporting cell migration, and refined disease mechanism through pAMPK-dependent control of CNBP stability.

    Evidence Direct CNBP-3'UTR and CNBP-KIF1C binding assays, mRNA localization and KIF1C recruitment loss-of-function; Co-IP of CNBP-pAMPK with AMPK-activator rescue in DM2 fibroblasts and Cnbp KO mouse imaging

    PMID:39807631 PMID:39982819

    Open questions at the time
    • AMPK phosphosite on CNBP not mapped
    • Full repertoire of protrusion-targeted CNBP mRNAs incomplete
    • How trafficking, translation and transcription roles are partitioned in a cell unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CNBP's multiple, sometimes opposing activities — G4 folding vs unfolding, transcriptional vs translational vs trafficking control — are coordinated and switched within a single cell.
  • No unifying model reconciling G4-promoting (c-myc) and G4-unfolding (KRAS, NOGGIN) activities
  • No high-resolution structure of CNBP bound to nucleic acid or partner proteins
  • Signal-specific phosphorylation code governing CNBP localization and function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0045182 translation regulator activity 5 GO:0140098 catalytic activity, acting on RNA 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2 GO:0005730 nucleolus 1 GO:0005840 ribosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 2 R-HSA-162582 Signal Transduction 1
Partners
AMPKKIF1CKPNB1NM23-H2PABPPCBP2RO60SMARCC2
Complex memberships
CNBP-KIF1C motor-adaptor complexCNBP-LAST lncRNA complexCNBP-PCBP2 holo-ITAF (ODC IRES)CNBP/NM23-H2 c-myc promoter complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Recombinant GST-CNBP fusion protein binds to G-rich single-stranded RNA and DNA in a sequence-specific manner, establishing CNBP as a sequence-specific single-stranded nucleic acid binding protein. In vitro binding assay with recombinant GST-fusion protein DNA research Medium 7788528
1998 CNBP binds to the 5'UTR of ribosomal protein mRNAs (specifically a downstream region) as a dimer, with binding mutually exclusive with La protein binding; Ro60 autoantigen is required as an ancillary factor for CNBP binding. CNBP multimerizes and its binding is assisted by a protease-sensitive factor involving Ro60. In vitro binding assays, RNA-protein binding analysis, mutational analysis of 5'UTR Journal of molecular biology Medium 9710533
2003 CNBP protein localizes to the nucleus of cells and strongly stimulates cell proliferation and increases c-myc promoter activity upon overexpression; CNBP is essential for forebrain induction in mouse embryos, and Myc expression was absent in anterior regions of Cnbp-/- embryos, indicating CNBP targets Myc in rostral head formation. Promoter-trap mutagenesis, transgenic rescue, CAT assay, in vivo mouse knockout Development (Cambridge, England) High 12588852
2003 CNBP and La proteins bind the 5'UTR of ribosomal protein mRNAs and can relieve TOP-mediated translational repression; CNBP binding to TOP hairpin structures activates translation of ribosomal protein mRNAs, and CNBP also increases cap-independent translation from IRES elements in mammalian cells. Tetracycline-regulated expression system, SEAP reporter assay in transgenic CHO cells, confocal microscopy Biotechnology and bioengineering Medium 12432575
2006 CNBP is required for forebrain specification in chick embryos at organogenesis stage; CNBP silencing abolished expression of forebrain transcription factors BF-1, Six3 and Hesx1 (but not Otx2), while CNBP misexpression induced their ectopic expression in the hindbrain, placing CNBP upstream of these rostral head transcription factors in a pathway parallel to Otx2. RNAi silencing and retroviral misexpression in chick embryos, in situ hybridization Developmental biology Medium 16626683
2007 ZNF9/CNBP and PCBP2 form a holo-ITAF ribonucleoprotein complex that binds the ODC mRNA IRES and stimulates cap-independent translation; ZNF9 specifically associates with wild-type but not mutant IRES sequences. Proteomics screen (mass spectrometry), biochemical validation of RNA-protein interaction, functional translation assays, co-immunoprecipitation of ZNF9 and PCBP2 Molecular & cellular proteomics High 17327219
2007 CNBP mediates neural crest cell expansion by controlling cell proliferation and survival rather than via cell fate switching during rostral head development in zebrafish; morpholino knockdown caused forebrain truncation, reduced proliferation, and increased cell death in anterior regions. Antisense morpholino oligonucleotide knockdown in zebrafish, in situ hybridization, cell proliferation and death assays Journal of cellular biochemistry Medium 17471504
2007 Haploinsufficiency of Znf9 in mice (Znf9+/- mice with significantly decreased Znf9 expression) causes myotonic dystrophy-like phenotype including myotonic discharges, heart conduction abnormalities, and muscle histological changes; Clc1 (skeletal muscle chloride channel 1) expression was dramatically decreased in Znf9+/- mice, and Znf9 transgenic rescue normalized both Znf9, Clc1 and the phenotype. Mouse genetics (heterozygous knockout, transgenic rescue), EMG, ECG, Western blot, loss-of-function with specific molecular readout Journal of molecular biology High 17335846
2008 The RGG box of CNBP is essential for RNA-protein binding and nucleic acid chaperone activity; Zn knuckles are required but not individually essential for CNBP biochemical activities; removal of the RGG box allows weak ssDNA binding but abolishes RNA binding; mutants lacking the N-terminal region or RGG box act as dominant negatives in Xenopus neural crest development. Site-directed mutagenesis, recombinant protein expression/purification in E. coli, in vitro biochemical assays, gain- and loss-of-function in Xenopus embryos Journal of molecular biology High 18703071
2010 ZNF9/CNBP associates with actively translating ribosomes and directly binds the ODC mRNA IRES sequence to activate cap-independent translation in primary human myoblasts; this activity is reduced in myoblasts from a DM2 patient. Polysome profiling, ribosome isolation, direct RNA binding assays, functional IRES translation assay in primary human myoblasts PloS one High 20174632
2012 CNBP associates with the poly(A) binding protein and accumulates in stress granules during arsenite treatment of human cells, implicating CNBP in mRNA handling during stress. The yeast ortholog Gis2 shows RNA-dependent interactions with poly(A) binding protein and eIF4G and localizes to processing bodies and stress granules. Co-immunoprecipitation, subcellular localization (fluorescence microscopy), polysome/stress granule fractionation PloS one Medium 23285195
2013 Human CNBP specifically binds the G-rich sequence of c-myc NHE III1 region and promotes G-quadruplex formation; CNBP induces a transient decrease followed by an increase in c-myc transcription in vivo. The interaction of CNBP with NM23-H2 is responsible for the increase of c-myc transcription, establishing a G-quadruplex-related CNBP/NM23-H2 protein complex at the c-myc promoter. EMSA, CD spectroscopy, FRET, ChIP, RNA interference, luciferase reporter assay, SPR, co-immunoprecipitation, co-transfection Biochimica et biophysica acta High 23774591
2013 CNBP acts as a transcriptional regulator of tbx2b, smarca5, and wnt5b in developing zebrafish embryos; CNBP up-regulates tbx2b and smarca5 and down-regulates wnt5b. The direct interaction between CNBP and candidate gene promoters was confirmed by EMSA and ChIP. CNBP DNA-binding sites are G-enriched sequences with high frequency of putative G-quadruplex secondary structure. Yeast one-hybrid assay, bioinformatics, EMSA, ChIP, loss-of-function in zebrafish PloS one Medium 23667590
2013 In Drosophila, CNBP regulates dMyc translation through an IRES-dependent mechanism; knockdown of dCNBP reduces dMyc protein but not mRNA levels; reintroduction of dMyc in CNBP-deficient wing imaginal discs rescues wing size reduction, establishing a CNBP-Myc translational axis controlling wing development. Drosophila genetics (knockdown, rescue experiments), Western blot, RT-PCR, wing size measurement, genetic epistasis Cell cycle Medium 24275942
2013 Tag-free recombinant CNBP forms homodimers that coexist with monomers; CNBP has a secondary structure dominated by random-coil and β-sheet corresponding to zinc knuckle motifs; CNBP structural stability increases upon binding single-stranded nucleic acid targets; a conserved tryptophan residue is involved directly or indirectly in nucleic acid binding. Size-exclusion HPLC, circular dichroism spectroscopy, fluorescence spectroscopy, recombinant protein purification Protein expression and purification Medium 24161561
2014 CNBP modulates transcription of Wnt signaling pathway components (cdk14, ptk7, tcf7l2) in a dose-dependent fashion in developing zebrafish embryos, which in turn affects c-myc, ccnd1 and axin2 expression. CNBP down-regulates Wnt5 transcription. Loss-of-function in zebrafish, RT-PCR, bioinformatics for CNBP binding site identification Biochimica et biophysica acta Medium 25151948
2017 CNBP acts as a transcription factor binding specific motifs in the promoter region of sustained inflammatory cytokines (particularly IL-6); LPS induces CNBP expression via NF-κB and autoregulation; LPS-induced phosphorylation-mediated CNBP dimerization is required for its nuclear translocation; cnbp-depleted zebrafish are highly susceptible to Shigella flexneri infection. ChIP, dual-luciferase assay, zebrafish knockdown, nuclear translocation assays, infection model Nucleic acids research High 28168305
2017 CNBP cooperates with lncRNA LAST to bind the 5'UTR of CCND1 mRNA and protect it from nuclease degradation, stabilizing CCND1 mRNA. CNBP RIP-seq and LAST RNA-seq identified CCND1 mRNA and three additional mRNA targets as post-transcriptional targets of the CNBP-LAST complex. RIP-seq, RNA-seq, CNBP-LAST binding assay, mRNA stability assays, xenograft model eLife Medium 29199958
2018 CNBP resides in the cytosol of macrophages and translocates to the nucleus in response to microbial pathogens and pathogen-derived products; nuclear translocation and DNA-binding activity of c-Rel (a driver of IL-12β transcription) requires CNBP; Cnbp-deficient macrophages exhibit impaired c-Rel activation without affecting canonical NF-κB/Rel signaling; Cnbp-deficient mice show reduced IL-12β and impaired Th1 IFN-γ response. Cnbp knockout mice, nuclear translocation assays, c-Rel DNA binding assay, infection model (toxoplasmosis), cytokine measurements The Journal of experimental medicine High 30442645
2019 CNBP acts in vitro as a G-quadruplex (G4)-unfolding protein over tetramolecular G4 formed by TG4T and over G4s in promoters of oncogenes (KRAS, NOGGIN); CNBP depletion reduces KRAS transcription in cellulo, suggesting CNBP relieves G4-mediated transcriptional silencing; CNBP unfolds the G4 in the NOG promoter and represses NOG transcription in zebrafish, establishing a G4-unfolding mechanism for CNBP transcriptional control. In vitro G4-unfolding assay, CNBP depletion in cells, RT-qPCR, zebrafish in vivo experiments Nucleic acids research High 31219592
2020 CNBP binding to lncRNA Braveheart (Bvht) remodels the 3-D structure of Bvht; Bvht has a well-defined but flexible 3-D structure in solution that changes upon CNBP binding; CNBP binding requires multiple domains of Bvht and the RHT/AGIL RNA motif, which contains a highly flexible loop surrounded by ordered helices. Small angle X-ray scattering (SAXS), structural ensemble analysis Nature communications High 31919376
2021 Drosophila CNBP (dCNBP) controls polyamine metabolism by binding dOdc mRNA and regulating its translation; depletion of dCNBP in muscles reduces ODC protein and polyamine levels, causing age-dependent locomotor defects; locomotor defects are rescued by polyamine supplementation or dOdc1 overexpression. The CNBP-polyamine axis is also reduced in muscles from DM2 patients. Drosophila muscle-specific knockdown, mRNA binding assays, ODC and polyamine measurements, locomotor assays, rescue experiments, analysis of DM2 patient muscle eLife High 34517941
2021 CNBP binds and promotes unfolding of G-quadruplexes formed by both positive-sense and negative-sense RNA strands of SARS-CoV-2; CNBP is the main human cellular protein bound to SARS-CoV-2 RNA genome. Multiple biophysical techniques (confirmed G4 formation), molecular binding approaches, G4-unfolding assays with purified CNBP International journal of molecular sciences Medium 33807682
2022 CNBP undergoes phosphorylation-induced nuclear translocation in response to RNA sensing pathways; nuclear CNBP binds IFNβ enhancer DNA and activates IFNβ gene transcription during SARS-CoV-2 infection; CNBP also binds SARS-CoV-2 viral RNA directly and competes with the nucleocapsid (N) protein to prevent viral RNA and N protein from undergoing liquid-liquid phase separation (LLPS), limiting viral replication. CNBP-deficient mice have higher viral loads and succumb rapidly to infection. CNBP-deficient mice, viral load measurement, direct RNA binding assay, LLPS competition assay, IFNβ reporter/transcription assay Research square (preprint)preprint Medium 35547851
2023 KPNB1 (karyopherin subunit beta 1) is responsible for nuclear transport of CNBP; liquid condensates (phase separation) of CNBP repress SWI/SNF core subunit SMARCC2 activity via direct interaction, leading to increased SMARCC1/SMARCA4 binary complex activity that facilitates 18S rRNA processing; blocking CNBP phase separation with a cell-penetrating peptide inhibits ribosome biogenesis. Co-immunoprecipitation, mass spectrometry, ChIP, dual-luciferase reporter assay, cell-penetrating peptide functional assay, gain- and loss-of-function in neuroblastoma cells Clinical and translational medicine Medium 37186134
2024 CNBP transcriptionally regulates TCOF1 by binding G-quadruplex sequences (PQSs) in its promoter; CNBP binds both G4-folded and unfolded forms of TCOF1 promoter PQS sequences with nM affinity in vitro; ChIP confirms CNBP binding to TCOF1 promoter in HeLa cells; in zebrafish, both cnbp overexpression and knockdown induce nolc1 (TCOF1 ortholog) transcription, suggesting CNBP modulates TCOF1 transcription through G-quadruplex folding/unfolding. Circular dichroism, fluorescence binding assays, ChIP in HeLa cells, luciferase reporter assay, zebrafish morpholino knockdown/overexpression, antisense oligonucleotide G4 disruption Scientific reports High 38553547
2025 CNBP forms a motor-adaptor complex with the KIF1C kinesin; CNBP directly binds GA-rich sequences in the 3'UTR of protrusion-targeted mRNAs; CNBP interacts with KIF1C and is required for KIF1C recruitment to mRNA cargo and active transport of mRNAs on microtubules to peripheral protrusions of mammalian cells; this trafficking is important for cell migration. Direct RNA binding assays (CNBP-3'UTR interaction), protein-protein interaction assays (CNBP-KIF1C), mRNA localization assays, loss-of-function with specific readout (mRNA trafficking, KIF1C recruitment) Cell reports High 39982819
2025 CNBP protein stability is regulated by pAMPK-dependent phosphorylation; CNBP interacts with pAMPK; in DM2 cells active pAMPK is reduced, leading to decreased CNBP stability; treatment with AMPK activator A769662 corrects CNBP stability and normalizes CNBP target expression in DM2 fibroblasts. Co-immunoprecipitation (CNBP-pAMPK), Western blot for pAMPK levels, small molecule AMPK activator treatment in DM2 fibroblasts, Cnbp KO mouse MRI/DTI analysis Human molecular genetics Medium 39807631

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science (New York, N.Y.) 937 11486088
2019 Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation. Molecular cancer 183 31718709
2005 Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 162 15735689
2017 LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells. eLife 79 29199958
2007 Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy. Journal of molecular biology 72 17335846
2020 Zinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution. Nature communications 67 31919376
2003 The zinc-finger protein CNBP is required for forebrain formation in the mouse. Development (Cambridge, England) 64 12588852
1998 Involvement of the Xenopus laevis Ro60 autoantigen in the alternative interaction of La and CNBP proteins with the 5'UTR of L4 ribosomal protein mRNA. Journal of molecular biology 64 9710533
2010 Mutant (CCTG)n expansion causes abnormal expression of zinc finger protein 9 (ZNF9) in myotonic dystrophy type 2. The American journal of pathology 61 20971734
2010 CNBP: a multifunctional nucleic acid chaperone involved in cell death and proliferation control. IUBMB life 57 20960530
2019 CNBP controls transcription by unfolding DNA G-quadruplex structures. Nucleic acids research 51 31219592
2007 The myotonic dystrophy type 2 protein ZNF9 is part of an ITAF complex that promotes cap-independent translation. Molecular & cellular proteomics : MCP 46 17327219
2005 Effect of the [CCTG]n repeat expansion on ZNF9 expression in myotonic dystrophy type II (DM2). Biochimica et biophysica acta 41 16376058
2017 CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6. Nucleic acids research 40 28168305
2013 Mechanistic studies for the role of cellular nucleic-acid-binding protein (CNBP) in regulation of c-myc transcription. Biochimica et biophysica acta 39 23774591
2003 Molecular cloning, developmental expression, promoter analysis and functional characterization of the mouse CNBP gene. Gene 38 12706888
2021 CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands. International journal of molecular sciences 37 33807682
2018 CNBP controls IL-12 gene transcription and Th1 immunity. The Journal of experimental medicine 36 30442645
2007 CNBP mediates neural crest cell expansion by controlling cell proliferation and cell survival during rostral head development. Journal of cellular biochemistry 35 17471504
2011 Saccharomyces cerevisiae Gis2 interacts with the translation machinery and is orthogonal to myotonic dystrophy type 2 protein ZNF9. Biochemical and biophysical research communications 33 21277287
2011 RNA Foci, CUGBP1, and ZNF9 are the primary targets of the mutant CUG and CCUG repeats expanded in myotonic dystrophies type 1 and type 2. The American journal of pathology 33 21889481
1995 Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA. DNA research : an international journal for rapid publication of reports on genes and genomes 32 7788528
2016 Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes. Cell death & disease 31 27711076
2006 CNBP regulates forebrain formation at organogenesis stage in chick embryos. Developmental biology 31 16626683
2003 Novel CNBP- and La-based translation control systems for mammalian cells. Biotechnology and bioengineering 30 12432575
2010 ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2. PloS one 26 20174632
2008 Dissecting CNBP, a zinc-finger protein required for neural crest development, in its structural and functional domains. Journal of molecular biology 26 18703071
2012 Yeast Gis2 and its human ortholog CNBP are novel components of stress-induced RNP granules. PloS one 25 23285195
2011 Myotonia congenita and myotonic dystrophy in the same family: coexistence of a CLCN1 mutation and expansion in the CNBP (ZNF9) gene. Clinical genetics 24 21204798
2014 CNBP modulates the transcription of Wnt signaling pathway components. Biochimica et biophysica acta 23 25151948
2004 A long PCR-based molecular protocol for detecting normal and expanded ZNF9 alleles in myotonic dystrophy type 2. Diagnostic molecular pathology : the American journal of surgical pathology, part B 23 15322428
2022 Characterization of full-length CNBP expanded alleles in myotonic dystrophy type 2 patients by Cas9-mediated enrichment and nanopore sequencing. eLife 22 36018009
2011 Upgrading molecular diagnostics of myotonic dystrophies: multiplexing for simultaneous characterization of the DMPK and ZNF9 repeat motifs. Molecular and cellular probes 22 21550396
2021 What's new about CNBP? Divergent functions and activities for a conserved nucleic acid binding protein. Biochimica et biophysica acta. General subjects 20 34474118
2005 Expression pattern and developmental behaviour of cellular nucleic acid-binding protein (CNBP) during folliculogenesis and oogenesis in fish. Gene 20 16002243
2000 cDNA cloning and developmental expression of cellular nucleic acid-binding protein (CNBP) gene in Xenopus laevis. Gene 20 10607896
2021 Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function. eLife 18 34517941
2013 CNBP regulates wing development in Drosophila melanogaster by promoting IRES-dependent translation of dMyc. Cell cycle (Georgetown, Tex.) 17 24275942
2013 Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development. PloS one 16 23667590
2009 The myotonic dystrophy type 2 (DM2) gene product zinc finger protein 9 (ZNF9) is associated with sarcomeres and normally localized in DM2 patients' muscles. Neuropathology and applied neurobiology 16 20102514
2023 Therapeutic targeting of CNBP phase separation inhibits ribosome biogenesis and neuroblastoma progression via modulating SWI/SNF complex activity. Clinical and translational medicine 15 37186134
2022 CircPACRGL promoted cell proliferation, migration and invasion as well as inhibited cell apoptosis in colorectal cancer via regulation of the miR-330-3p/CNBP axis. Molecular and cellular biochemistry 13 36459268
2017 Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients. Biochimica et biophysica acta. Molecular basis of disease 13 29291944
2018 CNBP Homologues Gis2 and Znf9 Interact with a Putative G-Quadruplex-Forming 3' Untranslated Region, Altering Polysome Association and Stress Tolerance in Cryptococcus neoformans. mSphere 11 30089646
2010 APP(DeltaNL695) expression in murine tissue downregulates CNBP expression. Neuroscience letters 11 20621159
2000 Protection induced in mice vaccinated with recombinant collagen-binding protein (CnBP) and alpha-toxoid against intramammary infection with Staphylococcus aureus. Microbiology and immunology 11 10888356
2020 Upregulation of lncRNA SUMO1P3 promotes proliferation, invasion and drug resistance in gastric cancer through interacting with the CNBP protein. RSC advances 9 35497433
2022 CircFMN2 Boosts Sorafenib Resistance in Hepatocellular Carcinoma Cells via Upregulating CNBP by Restraining Ubiquitination. Journal of oncology 8 35909906
2024 OSBPL10-CNBP axis mediates hypoxia-induced pancreatic cancer development. BioFactors (Oxford, England) 7 39329194
2013 Novel high-performance purification protocol of recombinant CNBP suitable for biochemical and biophysical characterization. Protein expression and purification 7 24161561
2025 A KIF1C-CNBP motor-adaptor complex for trafficking mRNAs to cell protrusions. Cell reports 6 39982819
2021 A 14-Year Italian Experience in DM2 Genetic Testing: Frequency and Distribution of Normal and Premutated CNBP Alleles. Frontiers in genetics 5 34234810
2008 Expression pattern of cellular nucleic acid-binding protein (CNBP) during embryogenesis and spermatogenesis of gibel carp. Molecular biology reports 5 18758991
2024 STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer. Biology direct 4 39080743
2022 CNBP restricts SARS-CoV2 by regulating IFN and disrupting RNA-protein condensates. Research square 4 35547851
2024 CircPRMT5 promotes progression of osteosarcoma by recruiting CNBP to regulate the translation and stability of CDK6 mRNA. PloS one 3 38626179
2024 circTADA2A inhibited SLC38A1 expression and suppresses melanoma progression through the prevention of CNBP trans-activation. PloS one 3 38635778
2022 Expression of concern: Upregulation of lncRNA SUMO1P3 promotes proliferation, invasion and drug resistance in gastric cancer through interacting with the CNBP protein. RSC advances 3 35427101
2004 Characterization of a single nucleotide polymorphism in the ZNF9 gene and analysis of association with myotonic dystrophy type II (DM2) in the Italian population. Molecular and cellular probes 3 15652222
2024 Co-occurrence of CAPN3 homozygous mutation and CCTG expansion in the CNBP gene in a patient with muscular dystrophy. Postepy psychiatrii neurologii 2 39119544
2024 Updated Structure of CNBP Repeat Expansions in Patients With Myotonic Dystrophy Type 2 and Its Implication for Standard Diagnostics. Neurology. Genetics 2 39703464
2024 The transcription of the main gene associated with Treacher-Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP). Scientific reports 1 38553547
2026 A new candidate tumor suppressor tRF-Ser inhibits gastric cancer progression by regulating the CNBP/HSPA8 axis. Cell death & disease 0 41881984
2026 Non-telomeric function deficiency of TERT enhances pressure overload-induced mouse cardiac remodeling by activation of CNBP-mediated THBS3/ITGB1 pathway. Acta pharmacologica Sinica 0 41882094
2026 Single-cell and spatial profiling of peripheral blood and synovium unveils pro-arthritis CNBP+ myeloid cells. Journal of translational medicine 0 41928282
2026 The novel (TCTG)n motif in CNBP expanded alleles: composition, dynamics and genotype-phenotype correlation in Myotonic dystrophy type 2 (DM2). Human genomics 0 41937177
2026 Dietary targeting of CNBP to rein in the EREG-EGFR cascade and restore homeostasis in colitis-associated colorectal cancer. International journal of biological sciences 0 41943842
2025 The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2. Human molecular genetics 0 39807631
2024 A KIF1C-CNBP motor-adaptor complex for trafficking mRNAs to cell protrusions. bioRxiv : the preprint server for biology 0 38979199

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