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Showing NUCLEOLIN — NCL is a alias.

NUCLEOLIN

Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 48 extracted findings
Cross-family judge faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Nucleolin (NCL/C23) is a multidomain nucleolar phosphoprotein that couples ribosomal DNA transcription, pre-rRNA processing, and ribosome assembly to a broad set of nucleic-acid recognition activities through its tandem RNA-binding domains (RBD1–4) and C-terminal RGG domain (PMID:3790520, PMID:11397095, PMID:40245140). It localizes to the fibrillar regions of the nucleolus during interphase and stays associated with NOR/rDNA structures throughout mitosis (PMID:6206987, PMID:6345184), where it binds pre-rRNA in preribosomal RNP particles (PMID:3790520); the conserved yeast ortholog NSR1 is required for 35S pre-rRNA processing and 40S subunit formation, establishing this ribosome-biogenesis role across eukaryotes (PMID:1706724, PMID:1508189, PMID:1644811, PMID:1644812). At rDNA, nucleolin is selectively required for RNA polymerase I transcription of chromatin templates and maintains a euchromatic, transcriptionally active state by antagonizing TTF-1 binding and the recruitment of TIP5/HDAC1-mediated repressive heterochromatin (PMID:17130237, PMID:22859736). Its activity is governed by cell-cycle-coupled phosphorylation—by casein kinase II on N-terminal acidic-domain serines during interphase and by Cdc2/CDK1 on TPXK threonine motifs during mitosis, the latter directing nucleolin to spindle poles and proper kinetochore-microtubule attachment (PMID:3427111, PMID:3190709, PMID:2192260, PMID:17535846). Through concerted action of its RBD and RGG domains, nucleolin recognizes G-quadruplex structures, demonstrated at atomic resolution for the MYC promoter G4, where all four RBDs engage the folded quadruplex (PMID:32191439, PMID:40245140). Beyond rRNA, nucleolin regulates gene expression post-transcriptionally: it represses p53 mRNA translation by binding a 5'–3'-UTR interaction region and homodimerizing through its RNA-binding domain, an interaction disrupted by RPL26 (PMID:22433872); it participates in microprocessor-dependent miRNA maturation with Drosha/DGCR8 (PMID:22049078); and it stabilizes bound mRNAs as part of higher-order ribonucleoprotein assemblies (PMID:35654044). A second functional pool is trafficked to the cell surface by a non-conventional, ER-Golgi-independent, actin-dependent route, where it serves as a receptor or co-receptor mediating ligand internalization for endostatin, viral capsids (EV71, RHDV), C1QTNF4, LPS, and apoptotic cells (PMID:11112338, PMID:17615292, PMID:25673703, PMID:30339712, PMID:33676896, PMID:21309751). Nucleolin abundance and activity are further tuned by additional post-translational modifications, including AMPK-mediated S328 phosphorylation that sequesters it in the nucleus to inhibit miRNA processing, P300-catalyzed K477 lactylation that redirects splicing, and TRIM21-mediated K48 ubiquitination targeting it for proteasomal degradation (PMID:31182601, PMID:38679071, PMID:38357830).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1984 High

    Established where nucleolin resides and that it remains tethered to rDNA-bearing structures through the cell cycle, anchoring its connection to ribosomal gene loci.

    Evidence Silver staining and immunoelectron microscopy across interphase and mitosis in hepatoma and PtK2 cells

    PMID:6206987 PMID:6345184

    Open questions at the time
    • Localization alone did not define a molecular activity
    • Did not address what nucleolin binds at NORs
  2. 1986 High

    Showed nucleolin physically associates with nascent pre-rRNA in preribosomal particles, providing the first direct molecular link to ribosome biogenesis.

    Evidence UV cross-linking and immunoprecipitation with rDNA probe hybridization from purified nucleoli

    PMID:3790520

    Open questions at the time
    • Did not define which RNA-binding domains mediate binding
    • Processing role not yet functionally demonstrated
  3. 1990 High

    Resolved nucleolin as a dually phosphorylated protein—CKII on interphase serines and Cdc2 on mitotic TPXK threonines—linking its modification state to cell-cycle context.

    Evidence In vitro CKII and M-phase H1 kinase assays with peptide mapping compared to in vivo 32P labeling

    PMID:2192260 PMID:3190709 PMID:3427111

    Open questions at the time
    • Functional consequence of each phospho-state not established at the time
    • Did not link phosphorylation to specific binding partners
  4. 1992 High

    Genetic disruption of the yeast ortholog NSR1 demonstrated an evolutionarily conserved, essential role in pre-rRNA processing and 40S subunit production.

    Evidence nsr1 deletion with pulse-labeling, Northern blot, and ribosomal subunit gradient analysis in yeast

    PMID:1508189 PMID:1644811 PMID:1644812 PMID:1706724 PMID:8245119

    Open questions at the time
    • Mechanism of processing facilitation not defined
    • Conservation of mammalian processing function inferred rather than directly tested in mammals
  5. 1996 High

    Mapped a direct interaction between nucleolin and nucleophosmin/B23, defining a core nucleolar protein-protein contact and its responsible domains.

    Evidence Two-hybrid, reciprocal co-IP, and deletion mapping in HeLa extracts; cell-cycle-resolved cross-linking co-IP

    PMID:10503877 PMID:8620867

    Open questions at the time
    • Functional output of the NCL-B23 complex not fully defined
    • Loss of interaction during mitosis not mechanistically explained
  6. 2006 High

    Demonstrated that nucleolin is specifically required for RNA polymerase I transcription on chromatin and physically associates with rDNA, distinguishing a chromatin-dependent transcription role.

    Evidence In vitro chromatin transcription, ChIP, and siRNA knockdown

    PMID:17130237

    Open questions at the time
    • How nucleolin facilitates elongation on chromatin not resolved
    • Did not address the histone-mark mechanism
  7. 2012 High

    Defined the chromatin mechanism: nucleolin antagonizes TTF-1/TIP5/HDAC1-mediated repression to keep rDNA euchromatic and permit RNAP I progression.

    Evidence ChIP-seq, histone mark and RNAP I/UBF distribution analysis with siRNA knockdown

    PMID:22859736

    Open questions at the time
    • Direct competition with TTF-1 for binding sites not structurally resolved
    • Selectivity for unmethylated genes mechanism unexplained
  8. 2007 High

    Linked the mitotic Cdc2-phosphorylated pool of nucleolin to spindle organization and chromosome segregation fidelity, extending its role beyond the nucleolus.

    Evidence RNAi depletion with high-resolution microscopy and phospho-specific antibody localization

    PMID:17535846

    Open questions at the time
    • Molecular partners at spindle poles not identified
    • Mechanism connecting nucleolin to kinetochore-microtubule attachment unknown
  9. 2012 High

    Established nucleolin as a translational and post-transcriptional regulator beyond rRNA—repressing p53 mRNA via RBD-mediated dimerization reversed by RPL26, and supporting microprocessor-dependent miRNA maturation.

    Evidence Translation/RNA-binding/dimerization assays and domain dissection; in vitro miRNA processing with Drosha/DGCR8 co-IP

    PMID:22049078 PMID:22433872

    Open questions at the time
    • In vivo extent of p53 regulation across stress contexts not defined
    • Range of miRNAs dependent on nucleolin not comprehensively mapped
  10. 2000 High

    Identified a non-conventional, ER-Golgi-independent, actin-dependent route delivering nucleolin to the cell surface where it functions in ligand internalization, defining an extranuclear functional pool.

    Evidence Confocal/EM imaging with transport-inhibitor and actin-disruption studies plus antibody cross-linking

    PMID:11112338

    Open questions at the time
    • Molecular machinery of the non-conventional export route unknown
    • How surface targeting is regulated not defined
  11. 2023 Medium

    Showed surface nucleolin serves as a receptor/co-receptor for a structurally diverse ligand set, from angiogenesis regulators to viral capsids and innate-immune ligands, internalizing cargo into cells.

    Evidence Binding, knockdown, gain-of-function, domain-mapping, and in vivo studies for endostatin, EV71, RHDV VP60, C1QTNF4, LPS, mtDNA/CpG-DNA, and apoptotic cells

    PMID:16135517 PMID:17615292 PMID:21309751 PMID:25673703 PMID:30339712 PMID:31412132 PMID:33676896

    Open questions at the time
    • Identity of obligate coreceptors for most ligands unknown
    • Whether a single surface conformation accommodates all ligands unresolved
  12. 2025 High

    Provided atomic-resolution mechanism for G-quadruplex recognition, showing all four RBDs plus the linker and RGG cooperatively engage the MYC promoter G4 in cells, identifying G4s as primary cellular substrates.

    Evidence 2.6-Å crystal structure, NMR, binding affinity, and CUT&Tag in cells; preceded by photo-cross-linking loop-length analysis

    PMID:11397095 PMID:32191439 PMID:40245140

    Open questions at the time
    • Genome-wide functional consequences of G4 binding not fully cataloged
    • How G4 binding integrates with rDNA transcription and mRNA regulation unresolved
  13. 2024 Medium

    Expanded the post-translational control of nucleolin to lysine lactylation, AMPK phosphorylation, and TRIM21 ubiquitination, showing distinct modifications reroute its splicing, miRNA-processing, and stability functions in disease contexts.

    Evidence MS-based PTM mapping with writer-enzyme assays, phospho-mutant rescue, ubiquitination assays, and xenograft models

    PMID:29168431 PMID:31182601 PMID:38357830 PMID:38679071

    Open questions at the time
    • Interplay/hierarchy among the different PTMs not defined
    • Most PTM mechanisms shown in single disease models without broad validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How nucleolin's many activities—rDNA transcription, G4 recognition, mRNA regulation, and surface receptor function—are coordinately partitioned and switched by its modification state within a single cell remains unresolved.
  • No unified model linking PTM state to subcellular pool and substrate choice
  • Mechanism routing nucleolin between nuclear and surface pools incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0003677 DNA binding 4 GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 3 GO:0001618 virus receptor activity 2 GO:0045182 translation regulator activity 2
Localization
GO:0005886 plasma membrane 7 GO:0005730 nucleolus 3 GO:0000228 nuclear chromosome 2 GO:0005654 nucleoplasm 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-4839726 Chromatin organization 1
Partners
DGCR8DROSHAHTERTNPM1/B23PARNRPL26TP53TRIM21
Complex memberships
microprocessor (Drosha/DGCR8)uPAR-nucleolin-CK2 surface signaling complex

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 Nucleolin (protein C23) localizes to the fibrillar shell surrounding the fibrillar center and to the fibrillar center of the nucleolus during interphase, and remains associated with NOR-containing structures (rDNA) during mitosis, as determined by silver staining and immunolocalization in Novikoff hepatoma cells. Silver staining, immunofluorescence, immunoelectron microscopy Chromosoma High 6206987
1983 During mitosis, nucleolin (C23) remains associated with disappearing nucleoli through prophase, then reappears in prenucleolar bodies and subsequently the nucleolus during telophase, while B23 follows a distinct pattern; C23 co-localizes with silver-staining NOR proteins throughout mitosis. Dual immunofluorescence with anti-B23 and anti-C23 antibodies in PtK2 cells Experimental cell research High 6345184
1986 Nucleolin (C23) directly associates with rapidly labeled pre-rRNA (18S and 28S sequences) in preribosomal RNP particles, as demonstrated by UV cross-linking and immunoprecipitation from Novikoff hepatoma nucleoli. UV cross-linking, immunoprecipitation with anti-C23 antibody, dot-blot hybridization with rDNA probes, sucrose gradient fractionation Biochemistry High 3790520
1987 Nucleolin is a natural preferential substrate for a nucleolar casein kinase II (type NII). The kinase phosphorylates nucleolin in vitro at serine residues in two highly acidic tryptic fragments (A: residues 21–49; C: residues 180–221) near the amino terminus, at canonical CKII consensus sites. Co-purification, in vitro kinase assay, peptide mapping, Km/Vmax analyses Biochemistry High 3427111
1988 Phosphopeptide patterns from nucleolin phosphorylated by purified casein kinase II (CKII) in vitro are identical to those from nucleolin isolated from tumor cells grown with [32P]-phosphate, establishing nucleolin as a physiological CKII substrate with ~2 mol phosphate per mol nucleolin. In vitro phosphorylation, partial tryptic digest, comparison of in vitro vs. in vivo phosphopeptide patterns Biochemical and biophysical research communications High 3190709
1988 Microinjection of anti-C23 antibody into Chironomus salivary gland nuclei caused a 2–3.5-fold stimulation of 32P incorporation into 38S pre-rRNA, selectively for pre-rRNA without affecting extranucleolar RNA, indicating nucleolin acts as a negative regulator of rDNA transcription. Microinjection of anti-C23 antibody into nuclei, 32P labeling, RNA extraction and electrophoresis Experimental cell research Medium 3169130
1990 Nucleolin is phosphorylated on threonines at TPXK motifs in the amino-terminal domain by p34cdc2 (Cdc2 kinase) specifically during mitosis, distinct from the interphase CKII-mediated serine phosphorylation; the same sites used in vivo during mitosis were phosphorylated by M-phase H1 kinase in vitro. In vitro kinase assay with starfish M-phase H1 kinase, in vivo 32P labeling, phosphoamino acid analysis, peptide mapping Molecular and cellular biology High 2192260
1991 Yeast NSR1 (nucleolin ortholog) specifically binds nuclear localization sequences (NLS), contains two RNA recognition motifs, and is required for normal cell growth; disruption of NSR1 causes severe growth defect, establishing functional conservation with mammalian nucleolin. Affinity purification on NLS peptide column, gene disruption, immunofluorescence, antibody-based cloning The Journal of cell biology High 1706724
1992 Yeast NSR1 is required for pre-rRNA processing: nsr1 deletion blocks initial 35S pre-rRNA processing, nearly eliminates 20S pre-rRNA, reduces 18S rRNA, and disrupts the free 40S ribosomal subunit pool, demonstrating a conserved role of the nucleolin ortholog in ribosome biogenesis. Pulse-labeling of rRNA, Northern blot, sucrose gradient fractionation of ribosomal subunits, antibiotic sensitivity assay Molecular and cellular biology High 1508189
1992 Yeast NSR1 is required for pre-rRNA processing and ribosome biogenesis: nsr1 deletion strains accumulate 35S pre-rRNA, show slow processing of 35S, impaired 18S rRNA methylation, and a reduced 40S:60S ratio; cold shock greatly exacerbates the processing defect. Pulse-labeling, pulse-chase rRNA analysis, Northern blot, NSR1 cold-shock induction assay The Journal of biological chemistry High 1644811 1644812
1993 Nucleolar localization of NSR1 requires a bipartite NLS and is mediated redundantly by either the N-terminal acidic/serine-rich domain or both RNA recognition motifs (RRMs); point mutations in RNP consensus octamers cause nuclear mislocalization, and the RGG domain is necessary for nucleolar accumulation when one RNP octamer is mutated. Deletion analysis with beta-galactosidase fusion reporter, immunofluorescence, point mutagenesis The Journal of cell biology High 8245119
1994 Nucleolin functions as a transcriptional repressor of the acute-phase response gene alpha-1 acid glycoprotein (AGP); nucleolin was purified from mouse hepatoma cells as the B-motif-binding factor and biochemical studies confirmed its repressor activity. Affinity purification, amino acid sequence analysis, transcription assay, DNA-binding assay Molecular and cellular biology Medium 8065340
1996 Nucleolin (C23) interacts with nucleolar protein B23 (nucleophosmin); co-immunoprecipitation from HeLa nuclear extract with either anti-C23 or anti-B23 monoclonal antibodies confirmed the interaction, which requires residues 540–628 of C23 (the nucleolar localization region) and residues 194–239 of B23. Two-hybrid system, co-immunoprecipitation, deletion mutant binding studies European journal of biochemistry High 8620867
1999 B23 (nucleophosmin) and nucleolin (C23) interact in vivo during interphase and cytokinesis but not during prometaphase/metaphase; the interaction persists even after actinomycin D-induced translocation to the nucleoplasm, and mitotic phosphorylation of B23 alone does not explain loss of interaction during mitosis. Chemical cross-linking with DSP, co-immunoprecipitation, in vitro Cdc2 kinase phosphorylation of GST-B23 followed by co-IP Cancer letters Medium 10503877
2000 Cell-surface nucleolin is transported to the plasma membrane via an active, non-conventional pathway independent of the ER-Golgi complex; surface nucleolin clusters in an actin cytoskeleton-dependent manner upon antibody cross-linking and can be internalized, mediating intracellular import of ligands. Confocal and electron microscopy, antibody cross-linking experiments, inhibitor studies (low temperature, serum-free medium, glycoprotein transport inhibitors), actin disruption Experimental cell research High 11112338
2001 Nucleolin RBD1 and RBD2 together (RBD12), but neither alone, specifically recognize a stem-loop NRE (nucleolin recognition element) RNA structure; in the complex, the hairpin loop adopts a well-defined conformation distinct from the free RNA, with both loop E motif and hairpin loop interacting specifically with the protein. NMR spectroscopy of free and protein-bound RNA, titration of RBD1, RBD2, and RBD12 with sNRE Journal of molecular biology High 11397095
2002 Following cell stress (ionizing radiation, camptothecin, heat shock), nucleolin relocalizes from the nucleolus to the nucleoplasm in a p53-dependent manner; the p53 C-terminal regulatory domain is required for nucleolin-p53 complex formation and nucleolin mobilization, which is independent of p53 transactivation; nucleolin and p53 interact directly in vitro. Immunofluorescence, co-immunoprecipitation, in vitro binding assay with deletion mutants, p53-null and mutant cell lines Molecular and cellular biology High 12138209
2002 Activation of nucleolin RNA-binding activity after genotoxic stress (UV or ionizing radiation) is mediated by the stress-activated protein kinase p38; nucleolin was identified as a genotoxic stress-responsive RNA-binding protein that binds stress-responsive mRNAs. Purification, RNA binding assays, p38 inhibitor treatment, identification of 40 mRNA ligands Nucleic acids research Medium 12000845
2004 Nucleolin interacts with the telomerase reverse transcriptase subunit hTERT through its RNA-binding domain 4 and RGG domain, with the interaction also involving hTERC (telomerase RNA); this nucleolin-hTERT interaction is critical for nucleolar localization of hTERT. Co-immunoprecipitation, domain deletion mapping, immunofluorescence colocalization The Journal of biological chemistry Medium 15371412
2005 Nucleolin functions as a macrophage cell-surface receptor for early apoptotic cells bearing polylactosaminyl CD43; anti-nucleolin antibody or deletion of the antibody-binding region abolishes binding to early apoptotic cells; nucleolin-transfected HEK293 cells acquire ability to bind early apoptotic cells. Antibody blocking, nucleolin transfection of HEK293, deletion mutant analysis, competitive inhibition with oligosaccharides The Journal of biological chemistry Medium 16135517
2005 Extranuclear nucleolin undergoes complex N- and O-glycosylations; N-glycosylation sites were mapped to N317 and N492 within RNA-binding domains 1 and 3, respectively, suggesting glycosylation may regulate RNA-binding function. SDS-PAGE, mass spectrometry, tunicamycin treatment, lectin binding, exoglycosidase digestion, MALDI-TOF, monosaccharide composition analysis Biochemistry High 15823039
2006 Nucleolin is required for RNA polymerase I transcription of chromatin (but not naked DNA) templates in vitro, and is specifically associated by ChIP with rRNA genes transcribed by RNAP I but not RNAP II or III; siRNA knockdown of nucleolin specifically inhibits RNAP I transcription. In vitro chromatin transcription assay, ChIP, immunofluorescence, siRNA knockdown Molecular and cellular biology High 17130237
2007 Nucleolin depletion by RNAi results in disorganized nucleoli at interphase, prolonged cell cycle with misaligned chromosomes, syntelic kinetochore-microtubule attachments with reduced centromere stretching, and defects in spindle organization; during mitosis, CDC2-phosphorylated nucleolin associates with spindle poles from prometaphase to anaphase. RNAi depletion, high-resolution microscopy, antibody specific for CDC2-phosphorylated nucleolin, kinetochore-microtubule attachment analysis Journal of cell science High 17535846
2007 Endostatin specifically binds cell-surface nucleolin with high affinity; blockage or knockdown of nucleolin abolishes endostatin's antiendothelial activity in vitro and antiangiogenic/antitumor activity in vivo; endostatin is internalized into cell nuclei via nucleolin; endostatin inhibits mitosis-related phosphorylation of nucleolin in the nucleus. Binding assay, neutralizing antibody, siRNA knockdown, colocalization, internalization assay, in vivo tumor model Blood High 17615292
1999 Urokinase (uPA) induces formation of a signaling complex on the cell surface containing uPAR, nucleolin, and casein kinase 2; nucleolin and CK2 were isolated by affinity chromatography and co-localized with uPAR; uPA activates CK2 in this complex leading to nucleolin phosphorylation; blocking nucleolin or CK2 inhibits uPA-induced cell proliferation. Affinity chromatography, nano-electrospray MS, immunoblotting, laser scanning and immunoelectron microscopy, co-immunoprecipitation, in vitro kinase assay, cell proliferation assay Current biology High 10607589
2011 Nucleolin interacts with the miRNA microprocessor components DGCR8 and Drosha in the nucleus; nucleolin directly and specifically binds the primary miR-15a/16 transcript; nucleolin is required for primary-to-precursor miRNA processing of miR-15a/16 in vitro; nuclear localization of nucleolin is critical for this function. Overexpression and knockdown studies, in vitro processing assay with cell extracts, co-immunoprecipitation, direct RNA binding assay The Journal of biological chemistry High 22049078
2012 Nucleolin depletion increases H3K9me2 (heterochromatin mark) and decreases H4K12Ac and H3K4me3 (euchromatin marks) at rRNA genes; ChIP-seq shows nucleolin enrichment at rDNA coding and promoter regions, preferentially at unmethylated genes; nucleolin depletion causes RNAP I accumulation at the start of transcription units and decreased UBF along the gene; nucleolin antagonizes binding of TTF-1 at the T0 terminator, thereby inhibiting TIP5 and HDAC1 recruitment and repressive heterochromatin formation. ChIP-seq, ChIP, siRNA knockdown, histone mark analysis, RNAP I and UBF distribution analysis Nucleic acids research High 22859736
2012 Nucleolin suppresses p53 mRNA translation using both 5'- and 3'-UTRs; nucleolin binds the same 5'-3'-UTR interaction region critical for RPL26 recruitment; nucleolin oligomerizes (dimerizes) through its RNA-binding domain; RPL26 disrupts NCL dimerization; NCL's RNA-binding domain mediates both dimerization and translational repression, and is the domain that interacts with RPL26. Translation assays, RNA binding assays, co-immunoprecipitation, domain deletion and point mutation analysis, dimerization assay The Journal of biological chemistry High 22433872
2012 Nucleolin binds LINE-1 ORF2 IRES and functions as an IRES trans-acting factor (ITAF) for ORF2 translation; NCL knockdown specifically reduces ORF2 IRES activity, L1 and L1-assisted Alu retrotransposition without altering L1 RNA or ORF1 protein abundance. RNA affinity chromatography, RNAi knockdown, IRES activity assay, retrotransposition assay Nucleic acids research Medium 23161687
2011 HuR promotes nucleolin translation via the nucleolin 3'UTR without affecting mRNA levels; miR-494 inhibits nucleolin expression by enhancing NCL mRNA association with Argonaute-containing complexes and promoting NCL mRNA transport to processing bodies (PBs); HuR and miR-494 functionally compete to control nucleolin abundance. MS2-tagged 3'UTR pull-down, immunoprecipitation, HuR silencing, miR-494 transfection, P-body tracking, ribosome loading assay Molecular and cellular biology Medium 21859890
2015 Cell-surface nucleolin mediates EV71 binding and infection; EV71 interacts directly with nucleolin via the VP1 capsid protein; knockdown of nucleolin reduces EV71 binding, infection, and production; expression of human nucleolin on mouse cells confers EV71 infection. Glycoproteomics, immunoprecipitation with EV71 particles, anti-nucleolin antibody blocking, siRNA knockdown, gain-of-function expression in mouse cells Journal of virology High 25673703
2016 Nucleolin depletion reduces axonal levels of importin β1 mRNA and protein; subcellular sequestration of nucleolin or importin β1 enhances axonal growth and causes a subcellular shift in protein synthesis; nucleolin associates with importin β1 mRNA in axons and with kinesins for anterograde transport. RNAi/siRNA knockdown, subcellular fractionation, in situ hybridization, cell growth assays in neurons and fibroblasts Cell reports Medium 27477284
2017 NCL phosphorylation at six CK2 consensus sites in the N-terminus is required for activation of PARN deadenylase activity upon oncogenic stimuli and UV stress; NCL directly interacts with PARN; under non-stress conditions NCL forms complexes with p53 and HuR; phosphorylation state of NCL determines specificity of its protein-protein and protein-RNA interactions governing mRNA deadenylation. In vitro deadenylase assay, co-immunoprecipitation, phospho-mutant (NCL-6/S*A) analysis, RNA binding assay RNA biology Medium 29168431
2018 LINE1 RNA recruits nucleolin and Kap1/Trim28 to repress Dux (master activator of the 2-cell program) in ESCs; LINE1 RNA also mediates binding of nucleolin and Kap1 to rDNA, promoting rRNA synthesis; in pre-implantation embryos, LINE1 RNA is required for Dux silencing, rRNA synthesis, and exit from the 2-cell stage. RNA immunoprecipitation, ChIP, siRNA/shRNA knockdown, RNA FISH, embryo functional assays Cell High 29937225
2019 Binding of cellular nucleolin to the HCV core RNA G-quadruplex (G4) structure stabilizes the G4 and suppresses HCV replication; NCL co-localizes with HCV particles; HCV infection upregulates NCL; silencing NCL greatly enhances viral RNA replication. Direct binding assay (in vitro and in-cell), colocalization, NCL knockdown with viral replication assay, G4-mutant virus comparison Nucleic acids research Medium 30462330
2018 Nucleolin mediates RHDV internalization via clathrin-dependent endocytosis; NCL interacts specifically with RHDV capsid protein VP60 through NCL N-terminal residues 285–318 and VP60's DVN motif (472Asp-Val-Asn474); NCL also interacts with clathrin light chain A C-terminus; blocking the NCL-VP60 interaction with a DVN peptide markedly reduces virus internalization. Biochemical inhibitors, RNAi, co-immunoprecipitation, domain deletion analysis, competitive peptide inhibition, in vivo animal experiments PLoS pathogens High 30339712
2019 Shear stress-activated AMPK phosphorylates nucleolin at serine 328 (S328), which sequesters nucleolin in the nucleus and inhibits processing of miR-93 and miR-484 that target KLF2 and eNOS mRNAs; this identifies an AMPK-NCL-miR-93/miR-484 axis in endothelial mechanotransduction. In silico analysis, phosphorylation site mapping (S328), AMPK inhibitor and activator studies, anti-miR rescue experiments, posttranslational modification analysis Proceedings of the National Academy of Sciences of the United States of America Medium 31182601
2020 Nucleolin strongly and preferentially binds G-quadruplex structures with long central loops (5–9 nucleotides) over short-loop variants; photo-cross-linking identified a 15-amino acid fragment in helix α2 of RBD2 as a loop-contact site; the RGG domain participates in terminal guanine quartet recognition; thus NCL recognizes G4 via concerted action of RBD2 (loop) and RGG (quartet) domains. Binding assays, photo-cross-linking with BrU-modified G4 sequences, quantitative proteomics (LC-MS/MS), G4 ligand competition assays Biochemistry High 32191439
2022 A cysteine tRNA-derived fragment (5'-tRFCys) directly binds nucleolin and promotes its oligomerization into a higher-order ribonucleoprotein complex that stabilizes bound metabolic mRNAs (Mthfd1l and Pafah1b1) against exonucleolytic degradation, driving breast cancer metastasis. Small RNA profiling, direct binding assay, oligomerization assay, RNA stability assay, functional metastasis assays Molecular cell High 35654044
2014 Nucleolin directly activates NFκB signaling; nucleolin overexpression increases NFκB phosphorylation and upregulates DNMT1; NFκB inactivation diminishes DNMT1 promoter activity, establishing a nucleolin-NFκB-DNMT1 axis in leukemia. Forced expression and RNAi knockdown, NFκB reporter assay, DNMT1 promoter activity assay, Western blot, in vitro and in vivo proliferation/tumorigenesis assays Oncotarget Medium 25015109
2017 Nucleolin identifies nucleolin as binding partner of topoisomerase II-alpha (TopIIA); this interaction is mapped to RNA-binding domain 3 of nucleolin and is essential for blocking DNA damage and apoptosis; nucleolin silencing decreases TopIIA decatenation activity and enhances formation of TopIIA-DNA cleavable complexes in the presence of etoposide. Co-immunoprecipitation, domain deletion mapping, TopIIA decatenation assay, cleavable complex assay, siRNA knockdown with DNA damage assays Leukemia Medium 28690315
2024 Nucleolin is lactylated predominantly at lysine K477 by the acyltransferase P300 in response to glycolytic hyperactivity; K477 lactylation promotes efficient translation of MADD mRNA by preventing alternative splicing that generates a premature termination codon; the resulting MADD protein activates ERK signaling and drives iCCA tumor growth. Proteomics, mass spectrometry, macromolecule interaction studies, P300 acyltransferase assay, alternative splicing analysis, xenograft tumor model, clinical sample validation Journal of hepatology High 38679071
2021 Nucleolin acts as a cell-surface receptor for C1QTNF4; interaction is mediated by the second C1q-like domain of C1QTNF4 and the C-terminus of nucleolin; upon cell binding, C1QTNF4 is actively internalized in monocytes; nucleolin may act as a docking molecule with context-dependent coreceptors. Mass spectrometric analysis of cell-surface proteins, co-immunoprecipitation, domain deletion analysis, imaging flow cytometry internalization assay The Journal of biological chemistry Medium 33676896
2025 Crystal structure (2.6 Å) of nucleolin bound to the MYC promoter G-quadruplex (MycG4) reveals: MycG4 adopts a folded parallel three-tetrad structure with two K+ ions; RBD1, RBD2, and Linker12 interact with the 6-nt central loop and 5' flanking region; RBD3 and RBD4 bind the 1-nt loops (confirmed by NMR); all four RBDs are required for high-affinity MycG4 binding; CUT&Tag sequencing confirmed nucleolin binding to MycG4 in cells, suggesting G4s are primary cellular substrates of nucleolin. X-ray crystallography (2.6 Å), NMR spectroscopy, CUT&Tag sequencing, binding affinity measurements Science High 40245140
2024 The E3 ubiquitin ligase TRIM21 mediates K48-linked polyubiquitination and proteasomal degradation of nucleolin; circRNA circ0006646 protects nucleolin from TRIM21-mediated ubiquitination by preventing the TRIM21-NCL interaction. Multi-omics proteomics, co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, in vivo xenograft and lentivirus models Advanced science Medium 38357830
2011 Cell-surface nucleolin on alveolar macrophages directly binds LPS via affinity chromatography; LPS co-localizes with C23 on cell surface and in cytoplasm; siRNA knockdown of C23 reduces LPS internalization, LPS-induced NF-κB DNA binding, and TNF-α and IL-6 protein expression. LPS affinity chromatography, immunofluorescence colocalization, siRNA knockdown, NF-κB DNA binding assay, cytokine measurement Cell biology international Medium 21309751
2019 Nucleolin on the plasma membrane of cardiomyocytes binds mitochondrial DNA (mtDNA) with ~10-fold greater affinity than nuclear DNA; blocking nucleolin with midkine reduces IL-1β/TNF-α expression and inhibits cellular uptake of CpG-DNA; nucleolin inhibition with AS1411 reduces IL-6 release; nucleolin facilitates CpG-DNA internalization independently of classical endocytosis. Microscale thermophoresis (direct binding), immunofluorescence, nucleolin inhibitor (midkine and AS1411) studies, CpG-DNA uptake assay, cytokine measurement British journal of pharmacology Medium 31412132
2023 G-quadruplex structures in MALAT1 lncRNA (in the 3' region) are specifically bound by nucleolin and nucleophosmin; G4-disrupting G-to-A mutations in MALAT1 abolish localization of both NCL and NPM to nuclear speckles; truncated NCL (ΔNCL) binds all three MALAT1 rG4s with high affinity in vitro. rG4 domain-specific RNA pull-down, mass spectrometry, RNA immunoprecipitation, imaging, G-to-A mutagenesis, in vitro biophysical binding studies Nucleic acids research Medium 37558241

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Structure and functions of nucleolin. Journal of cell science 622 10036227
2018 A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity. Cell 420 29937225
1999 Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 399 10544174
2006 Nucleolin: a multiFACeTed protein. Trends in cell biology 287 17157503
1984 Silver staining, immunofluorescence, and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma 270 6206987
1983 Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Experimental cell research 224 6345184
2012 RNA-binding protein nucleolin in disease. RNA biology 221 22617883
2015 The roles of nucleolin subcellular localization in cancer. Biochimie 201 25866190
2007 Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin. Blood 200 17615292
2000 The cell-surface-expressed nucleolin is associated with the actin cytoskeleton. Experimental cell research 196 11112338
2017 New perspectives of physiological and pathological functions of nucleolin (NCL). Life sciences 191 28751161
2012 Human pathology in NCL. Biochimica et biophysica acta 187 23200925
1991 The NSR1 gene encodes a protein that specifically binds nuclear localization sequences and has two RNA recognition motifs. The Journal of cell biology 182 1706724
2013 NCL diseases - clinical perspectives. Biochimica et biophysica acta 176 23602993
1998 Nucleolin: a multifunctional major nucleolar phosphoprotein. Critical reviews in biochemistry and molecular biology 155 9918513
2002 Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation. Molecular and cellular biology 148 12138209
1987 Phosphorylation of nucleolin by a nucleolar type NII protein kinase. Biochemistry 145 3427111
1990 Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. Molecular and cellular biology 141 2192260
2015 Cell biology of the NCL proteins: What they do and don't do. Biochimica et biophysica acta 139 25962910
1996 C23 interacts with B23, a putative nucleolar-localization-signal-binding protein. European journal of biochemistry 139 8620867
2004 Current state of clinical and morphological features in human NCL. Brain pathology (Zurich, Switzerland) 130 14997938
1986 Association of protein C23 with rapidly labeled nucleolar RNA. Biochemistry 129 3790520
2012 Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase I transcription. Nucleic acids research 120 22859736
1992 NSR1 is required for pre-rRNA processing and for the proper maintenance of steady-state levels of ribosomal subunits. Molecular and cellular biology 120 1508189
2002 Identification of nucleolin and nucleophosmin as genotoxic stress-responsive RNA-binding proteins. Nucleic acids research 113 12000845
2007 Nucleolin functions in nucleolus formation and chromosome congression. Journal of cell science 111 17535846
2012 Interactions of nucleolin and ribosomal protein L26 (RPL26) in translational control of human p53 mRNA. The Journal of biological chemistry 106 22433872
2014 Cell surface nucleolin as a target for anti-cancer therapies. Recent patents on anti-cancer drug discovery 102 24251811
1995 The ncl-1 gene and genetic mosaics of Caenorhabditis elegans. Genetics 102 8582642
1994 Purification and characterization of nucleolin and its identification as a transcription repressor. Molecular and cellular biology 101 8065340
2006 Nucleolin is required for RNA polymerase I transcription in vivo. Molecular and cellular biology 100 17130237
2013 NCL disease mechanisms. Biochimica et biophysica acta 98 23707513
1992 Yeast NSR1 protein that has structural similarity to mammalian nucleolin is involved in pre-rRNA processing. The Journal of biological chemistry 96 1644811
2007 Functions of the histone chaperone nucleolin in diseases. Sub-cellular biochemistry 95 17484127
2011 Competitive regulation of nucleolin expression by HuR and miR-494. Molecular and cellular biology 94 21859890
2004 Nucleolin interacts with telomerase. The Journal of biological chemistry 93 15371412
2024 Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD. Journal of hepatology 92 38679071
2015 Cell surface nucleolin facilitates enterovirus 71 binding and infection. Journal of virology 91 25673703
2016 Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair. Biochemistry and cell biology = Biochimie et biologie cellulaire 87 27673355
1999 Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin. Current biology : CB 83 10607589
2016 Roles of nucleolin. Focus on cancer and anti-cancer therapy. Saudi medical journal 75 27874146
2012 hnRNPL and nucleolin bind LINE-1 RNA and function as host factors to modulate retrotransposition. Nucleic acids research 75 23161687
2016 Nucleolin-Mediated RNA Localization Regulates Neuron Growth and Cycling Cell Size. Cell reports 71 27477284
2022 A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of its bound metabolic mRNAs. Molecular cell 70 35654044
2014 Nucleolin: dual roles in rDNA chromatin transcription. Gene 68 25225127
1990 Genomic organization and chromosomal localization of the human nucleolin gene. The Journal of biological chemistry 67 2394707
2015 Towards a new understanding of NCL pathogenesis. Biochimica et biophysica acta 65 26026924
1993 Multiple regions of NSR1 are sufficient for accumulation of a fusion protein within the nucleolus. The Journal of cell biology 65 8245119
2015 Human anti-nucleolin recombinant immunoagent for cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 64 26170308
1992 Cold shock induction of yeast NSR1 protein and its role in pre-rRNA processing. The Journal of biological chemistry 62 1644812
2023 Anti-nucleolin aptamer AS1411: an advancing therapeutic. Frontiers in molecular biosciences 61 37808518
2011 Nucleolin protein interacts with microprocessor complex to affect biogenesis of microRNAs 15a and 16. The Journal of biological chemistry 61 22049078
2019 Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication. Nucleic acids research 60 30462330
2017 Multifaceted Nucleolin Protein and Its Molecular Partners in Oncogenesis. Advances in protein chemistry and structural biology 59 29459030
2005 A multifunctional shuttling protein nucleolin is a macrophage receptor for apoptotic cells. The Journal of biological chemistry 56 16135517
2023 Inducible Degradation of Oncogenic Nucleolin Using an Aptamer-Based PROTAC. Journal of medicinal chemistry 54 36608275
2005 Nucleolin undergoes partial N- and O-glycosylations in the extranuclear cell compartment. Biochemistry 51 15823039
2001 Recognition of pre-formed and flexible elements of an RNA stem-loop by nucleolin. Journal of molecular biology 50 11397095
2018 MECP2 Mutation Interrupts Nucleolin-mTOR-P70S6K Signaling in Rett Syndrome Patients. Frontiers in genetics 47 30619462
2017 A statistical view of protein chemical synthesis using NCL and extended methodologies. Bioorganic & medicinal chemistry 47 28578993
2022 Nucleolin: a cell portal for viruses, bacteria, and toxins. Cellular and molecular life sciences : CMLS 46 35503380
2014 A nucleolin-DNMT1 regulatory axis in acute myeloid leukemogenesis. Oncotarget 45 25015109
1988 Effects of anti-C23 (nucleolin) antibody on transcription of ribosomal DNA in Chironomus salivary gland cells. Experimental cell research 45 3169130
2009 Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress. The FEBS journal 44 20050922
2016 Nuclear Functions of Nucleolin through Global Proteomics and Interactomic Approaches. Journal of proteome research 43 27049334
1996 Developmental and cell cycle regulation of alfalfa nucMs1, a plant homolog of the yeast Nsr1 and mammalian nucleolin. The Plant cell 42 8721748
1999 In vivo interaction of nucleophosmin/B23 and protein C23 during cell cycle progression in HeLa cells. Cancer letters 39 10503877
1988 Nucleolin (C23), a physiological substrate for casein kinase II. Biochemical and biophysical research communications 37 3190709
2023 Identification of G-quadruplex structures in MALAT1 lncRNA that interact with nucleolin and nucleophosmin. Nucleic acids research 35 37558241
2020 Nucleolin Discriminates Drastically between Long-Loop and Short-Loop Quadruplexes. Biochemistry 35 32191439
2019 Nucleolin Is a Functional Binding Protein for Salinomycin in Neuroblastoma Stem Cells. Journal of the American Chemical Society 34 30689374
1984 Immunofluorescence studies on proteins B23 and C23 in nucleoli of human lymphocytes. Experimental cell research 34 6201372
2021 Cancer Stem Cells and Nucleolin as Drivers of Carcinogenesis. Pharmaceuticals (Basel, Switzerland) 33 33451077
2021 Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy. Journal of experimental & clinical cancer research : CR 33 34078433
2017 Targeting nucleolin for better survival in diffuse large B-cell lymphoma. Leukemia 33 28690315
2022 Nucleolin: a binding partner of G-quadruplex structures. Trends in cell biology 32 35410819
2021 Identification of RSV Fusion Protein Interaction Domains on the Virus Receptor, Nucleolin. Viruses 32 33567674
2018 Nucleolin and ErbB2 inhibition reduces tumorigenicity of ErbB2-positive breast cancer. Cell death & disease 30 29352243
2025 Structural basis for nucleolin recognition of MYC promoter G-quadruplex. Science (New York, N.Y.) 29 40245140
2019 Shear stress regulation of miR-93 and miR-484 maturation through nucleolin. Proceedings of the National Academy of Sciences of the United States of America 29 31182601
2019 Inhibiting nucleolin reduces inflammation induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and reoxygenation. British journal of pharmacology 29 31412132
2018 Nucleolin Overexpression Confers Increased Sensitivity to the Anti-Nucleolin Aptamer, AS1411. Cancer investigation 29 30396283
2017 Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response. RNA biology 29 29168431
2011 Cell-surface nucleolin is involved in lipopolysaccharide internalization and signalling in alveolar macrophages. Cell biology international 29 21309751
2009 Nucleolin/C23 is a negative regulator of hydrogen peroxide-induced apoptosis in HUVECs. Cell stress & chaperones 29 19757191
2024 Integrated Multiomics Reveals Silencing of has_circ_0006646 Promotes TRIM21-Mediated NCL Ubiquitination to Inhibit Hepatocellular Carcinoma Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 38357830
2020 Recognition of nucleolin through interaction with RNA G-quadruplex. Biochemical pharmacology 28 32860827
2011 DIGE-based proteomic analysis identifies nucleophosmin/B23 and nucleolin C23 as over-expressed proteins in relapsed/refractory acute leukemia. Leukemia research 28 21310483
2021 C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation. Oncogenesis 27 33731669
2018 Meeting the needs of breast cancer: A nucleolin's perspective. Critical reviews in oncology/hematology 27 29650282
1995 Immunodominant RNA recognition motifs of human nucleolin/C23. Molecular immunology 27 8559145
1997 Sphingolipid activator proteins (SAPs) in neuronal ceroid lipofuscinoses (NCL). Neuropediatrics 24 9151322
2019 Recent Insights into NCL Protein Function Using the Model Organism Dictyostelium discoideum. Cells 22 30717401
2018 Nucleolin mediates the internalization of rabbit hemorrhagic disease virus through clathrin-dependent endocytosis. PLoS pathogens 22 30339712
2021 Nucleolin acts as the receptor for C1QTNF4 and supports C1QTNF4-mediated innate immunity modulation. The Journal of biological chemistry 21 33676896
2020 A novel nucleolin-binding peptide for Cancer Theranostics. Theranostics 21 32802184
2019 Midkine promotes articular chondrocyte proliferation through the MK-LRP1-nucleolin signaling pathway. Cellular signalling 21 31639491
2016 p85α promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation. Oncotarget 21 26918608
2021 Targeting nucleolin by RNA G-quadruplex-forming motif. Biochemical pharmacology 19 33460627
2018 Nucleolin protects against doxorubicin-induced cardiotoxicity via upregulating microRNA-21. Journal of cellular physiology 19 29968904

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