Affinage

Showing NPM1 — NPM is a alias.

NPM1

Nucleophosmin · UniProt P06748

Length
294 aa
Mass
32.6 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 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

NPM1 (B23) is an abundant, predominantly oligomeric nucleolar phosphoprotein that functions as a molecular chaperone and nucleocytoplasmic shuttling hub coordinating ribosome biogenesis, centrosome duplication, and the p53/ARF tumor-suppressor network (PMID:10211837, PMID:7772597). As a chaperone it preferentially binds denatured substrates through exposed hydrophobic regions, preventing aggregation and protecting enzyme activity (PMID:10211837), and its oligomerization domain—centered on a conserved GSGP loop—is required for partner binding, protein stability, and nucleolar residency (PMID:16679321, PMID:7772597). Through this oligomeric scaffold NPM1 retains a network of nucleolar clients including ribosomal protein S9, PES1, NPM3, and the SUMO proteases SENP3/SENP5, and its loss disperses these factors and impairs rRNA processing and ribosome biogenesis (PMID:14729947, PMID:18420587, PMID:19015314, PMID:15596447, PMID:20011973). NPM1 governs centrosome/centriole duplication as a CDK2/cyclin E substrate that dissociates from unduplicated centrosomes upon phosphorylation, and as a Plk2 substrate phosphorylated on Ser4 during S-phase (PMID:11051553, PMID:20352051). It is a central node of the ARF–MDM2–p53 axis: ARF associates with NPM1 in megadalton particles and is sequestered in the nucleolus by oligomeric NPM1, while stress signals (DNA damage, SIRT7-mediated deacetylation, AKT-mediated Ser48 phosphorylation) redistribute NPM1 to the nucleoplasm where it binds MDM2 and stabilizes p53 and p21 (PMID:14729947, PMID:15485902, PMID:16267006, PMID:33495326, PMID:19221506, PMID:25071014). In acute myeloid leukemia, cytoplasmic-mislocalized mutant NPM1 (NPM1c) is required to maintain the leukemic state: it directly binds active chromatin co-occupied by KMT2A/MLL1, sustains a transcription hub, and inhibits histone deacetylase activity to drive HOXA/B and MEIS1 expression (PMID:30205049, PMID:36455613, PMID:36455589). NPM1 additionally tunes immune and metabolic programs by sequestering IRF1 to suppress MHC-I/II expression and by recruiting KDM5b to repress TSC1 and license mTOR-dependent inflammatory glycolysis (PMID:38390737, PMID:39402629).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 Medium

    Establishing that NPM1 is overwhelmingly oligomeric and biophysically stable defined the structural basis for its later role as a scaffold whose oligomerization state controls partner binding and localization.

    Evidence Native PAGE, sucrose gradient sedimentation, and chemical stability tests in HeLa cells

    PMID:7772597

    Open questions at the time
    • Did not resolve oligomer stoichiometry at atomic resolution
    • Did not connect oligomeric state to specific functional partners
  2. 1992 Medium

    Showing that drug-induced nucleolus-to-nucleoplasm redistribution of NPM1 is reversible and protein-synthesis-independent established that NPM1 function is governed by relocalization of existing protein rather than de novo expression.

    Evidence Camptothecin treatment with washout, cycloheximide chase, and crosslinking by immunocytochemistry

    PMID:1426041

    Open questions at the time
    • Did not identify the signal driving redistribution
    • Phosphorylation was explicitly ruled out as the trigger here, leaving the mechanism open
  3. 1999 High

    Demonstrating intrinsic chaperone activity against multiple substrates moved NPM1 from an abundant nucleolar marker to a functional protein-folding/anti-aggregation factor.

    Evidence In vitro turbidity, enzyme-protection, and refolding assays with multiple substrates

    PMID:10211837

    Open questions at the time
    • Physiological substrates in cells not defined
    • Link between chaperone activity and ribosome biogenesis not established here
  4. 2000 High

    Identifying NPM1 as a CDK2/cyclin E substrate that licenses centrosome duplication connected NPM1 phosphorylation to cell-cycle control of centrosome number.

    Evidence In vitro kinase assay, antibody microinjection, and non-phosphorylatable mutant in a centrosome duplication assay

    PMID:11051553

    Open questions at the time
    • Phosphosite mapping and downstream centrosomal effectors not fully resolved
    • Relationship to nucleolar pool unclear
  5. 2004 High

    Defining the ARF–NPM1 megadalton complex and the domains required for it placed NPM1 at the center of ARF-dependent control of rRNA processing and p53-independent growth arrest.

    Evidence TAP purification, co-IP, sucrose gradients, deletion mutants, and rRNA processing assays; ARF induction and S-phase assays

    PMID:14729947 PMID:15485902

    Open questions at the time
    • How MDM2 competition is regulated by upstream signals not fully defined
    • Distinction between nucleolar sequestration and shuttling effects partly correlative
  6. 2006 High

    Mapping the GSGP loop as essential for ARF binding, oligomerization, stability, and nucleolar localization unified NPM1's structural and regulatory functions into one motif.

    Evidence Site-directed mutagenesis with binding, ubiquitination, stability, and localization readouts

    PMID:16679321

    Open questions at the time
    • Whether the loop directly contacts ARF or acts indirectly via oligomerization not separated
    • Structural basis not resolved
  7. 2007 High

    Identifying NPM3, PES1, and Ebp1 as NPM1 interactors whose nucleolar localization or rRNA biogenesis depends on NPM1 built the picture of NPM1 as a nucleolar targeting/retention hub for ribosome-biogenesis factors.

    Evidence Yeast two-hybrid, co-IP, domain mapping, knockdown, and rRNA/ribosome biogenesis assays

    PMID:15596447 PMID:17951246 PMID:20011973

    Open questions at the time
    • Direct contribution of each client to mature ribosome output not quantified
    • SUMOylation-dependence of Ebp1 binding mechanistically incomplete
  8. 2008 High

    Showing NPM1 binds RPS9 and the SENP3/SENP5 SUMO proteases, and is required for their nucleolar accumulation, mechanistically tied NPM1 to nucleolar SUMO dynamics and ribosome biogenesis.

    Evidence RNA-independent co-IP (including Xenopus extracts), depletion, SUMO and nucleolar immunofluorescence, ribosome biogenesis assays

    PMID:18420587 PMID:19015314

    Open questions at the time
    • Whether NPM1 directly protects these clients or stabilizes a larger complex unclear
    • RPS9 study is single-lab Medium confidence
  9. 2008 High

    Demonstrating that nuclear Akt binds the NPM1 C-terminus and protects it from caspase-3 cleavage linked growth-factor/PI3K signaling to NPM1 stability and cell survival.

    Evidence Co-IP, deletion mapping, caspase-3 cleavage assay, isoform-specific knockdown, survival assays

    PMID:18931307

    Open questions at the time
    • Interplay between Akt2-regulated SUMOylation and Ser48 phosphorylation not fully integrated
    • In vivo relevance not tested here
  10. 2010 High

    Identifying Plk2 phosphorylation of NPM1 Ser4 during S-phase added a second cell-cycle kinase input controlling centriole copy number.

    Evidence In vitro kinase assay, Polo-box pull-down/co-IP, S4A/S4D mutants, centriole counting

    PMID:20352051

    Open questions at the time
    • Relationship between Ser4 (Plk2) and CDK2/cyclin E phosphorylation not resolved
    • Mechanism connecting phosphorylation to centriole machinery unknown
  11. 2014 Medium

    Showing AKT Ser48 phosphorylation blocks NPM1 oligomerization and shifts ARF to the nucleoplasm linked oligomeric state to the ARF–MDM2–p53 output and to a druggable AKT node.

    Evidence Co-IP, phospho-specific antibody, AKT inhibitor (MK-2206), and pancreatic xenograft

    PMID:25071014

    Open questions at the time
    • Single-lab Medium-confidence mechanism
    • How Ser48 phosphorylation antagonizes oligomerization structurally not defined
  12. 2021 High

    Establishing SIRT7-mediated deacetylation as the trigger for stress-dependent NPM1 relocation to the nucleoplasm and MDM2 binding defined a post-translational switch stabilizing p53 after UV damage.

    Evidence In vitro deacetylation, co-IP, localization, ATR kinase assay, SIRT7 knockout mouse, p53 ubiquitination assay

    PMID:33495326

    Open questions at the time
    • Specific acetyl-lysine residues controlling relocation not all mapped
    • Integration with phosphorylation-based relocation signals unresolved
  13. 2018 High

    Demonstrating that removing cytoplasmic NPM1c collapses HOX expression and drives AML differentiation proved NPM1c is an active, ongoing requirement for the leukemic state rather than an initiating event only.

    Evidence Degron-based targeted degradation, XPO1 inhibition, RNA-seq, mouse leukemia survival model

    PMID:30205049

    Open questions at the time
    • Did not yet show direct chromatin binding by NPM1c
    • Cofactors mediating HOX regulation not identified here
  14. 2023 High

    Genome-wide occupancy and rapid-degradation studies established that NPM1c directly binds active chromatin co-occupied by MLL1, sustains a transcription hub, and inhibits HDAC activity to maintain HOXA/B and MEIS1 expression.

    Evidence ChIP-seq, CUT&RUN, ATAC-seq, HDAC activity assay, targeted degradation, RNA-seq (two concurrent studies)

    PMID:36455589 PMID:36455613

    Open questions at the time
    • Direct DNA/chromatin contact mechanism of cytoplasmically-prone NPM1c not structurally defined
    • How aberrant cytoplasmic localization yields chromatin occupancy mechanistically incomplete
  15. 2024 High

    Linking oligomeric NPM1 to KDM5b recruitment at TSC1 and to IRF1 sequestration at MHC loci extended NPM1's scaffolding role into macrophage metabolic reprogramming and tumor immune evasion.

    Evidence Co-IP, ChIP-qPCR, macrophage-specific knockout mouse, metabolite profiling, IRF1 reporter and T-cell killing assays, RNA-seq

    PMID:38390737 PMID:39402629

    Open questions at the time
    • Whether these chromatin/transcription-factor controls share a common NPM1 surface unknown
    • Tissue-specificity of these programs not broadly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single oligomeric NPM1 scaffold integrates its chaperone, ribosome-biogenesis, centrosome, p53/ARF, and chromatin-regulatory functions through defined post-translational switches remains unresolved.
  • No unified structural model linking oligomerization state to each functional output
  • The hierarchy among acetylation, phosphorylation, and SUMOylation in directing localization is undefined
  • Direct chromatin-binding mechanism of NPM1c remains structurally uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0140313 molecular sequestering activity 3 GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1 GO:0044183 protein folding chaperone 1
Localization
GO:0005730 nucleolus 8 GO:0005654 nucleoplasm 5 GO:0005634 nucleus 3 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1640170 Cell Cycle 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-168256 Immune System 1
Partners
CDKN2A/ARFKMT2AMDM2NPM3PES1RPS9SENP3SENP5
Complex memberships
ARF-NPM1 megadalton particleNPM1-SENP3/SENP5NPM1c-MLL1/KMT2A chromatin complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 NPM1/B23 is a substrate of CDK2/cyclin E in centrosome duplication. NPM1 associates specifically with unduplicated centrosomes and dissociates upon CDK2/cyclin E-mediated phosphorylation. An anti-NPM1 antibody blocking this phosphorylation suppresses centrosome duplication initiation in vivo, and expression of a non-phosphorylatable NPM1 mutant blocks centrosome duplication. In vitro kinase assay, anti-NPM1 antibody microinjection, non-phosphorylatable mutant expression, centrosome duplication assay Cell High 11051553
1999 NPM1/B23 has molecular chaperone activity: it inhibits aggregation of multiple protein substrates (HIV-1 Rev, LADH, carboxypeptidase A, citrate synthase, rhodanese), protects enzyme activity during thermal denaturation, promotes refolding of guanidine-HCl-denatured LADH, and preferentially binds denatured substrates by exposing hydrophobic regions. Turbidity (light-scattering) aggregation assay, enzyme activity protection assay, refolding assay, hydrophobic probe binding Protein science High 10211837
2004 ARF tumor suppressor physically associates with NPM1 in high-molecular-weight (2–5 MDa) complexes. The interaction requires the ARF amino terminus (also needed for Mdm2 binding) and the central acidic domain plus adjacent oligomerization-regulating segment of NPM1. An NPM1 mutant lacking the C-terminal nucleic acid-binding domain oligomerizes with endogenous NPM1, prevents p19ARF from entering the 2–5 MDa particles, and overrides ARF-mediated retardation of rRNA processing. Tandem-affinity purification, co-immunoprecipitation, sucrose gradient sedimentation, deletion mutagenesis, rRNA processing assay Molecular and cellular biology High 14729947
2004 ARF upregulation in response to hyperproliferative signals leads to nucleolar retention of NPM1 and consequent cell cycle arrest via a p53-independent mechanism. Mdm2 outcompetes NPM1 for ARF binding, releasing NPM1 from ARF complexes in vitro and restoring S-phase progression in vivo. ARF sequesters NPM1 in the nucleolus without inhibiting rRNA processing but prevents its nucleocytoplasmic shuttling. Co-immunoprecipitation, cell cycle analysis (S-phase entry assay), siRNA knockdown, ARF induction system Molecular and cellular biology High 15485902
1997 The NPM portion of NPM-ALK mediates oncogenesis by enabling oligomerization and consequent kinase activation of the ALK moiety. NPM-ALK mutants lacking non-overlapping portions of the NPM segment each fail to form complexes, lack kinase activity in vivo, and fail to transform cells. Nuclear/nucleolar localization (mediated by NPM shuttling) is dispensable for oncogenesis; an engineered TPR-ALK dimerization-competent chimera transforms cells efficiently from the cytoplasm. Sedimentation gradient complex analysis, cell fractionation, kinase activity assays, transformation focus assay, immunostaining Molecular and cellular biology High 9121481
2008 NPM1/B23 associates with ribosomal protein S9 (RPS9) in an RNA-independent manner, requiring an intact B23 oligomerization domain. Overexpression of NPM1 facilitates nucleolar storage of S9, while knockdown of NPM1 leads to diminished nucleolar S9 levels, implicating NPM1 in protecting RPS9 to facilitate ribosome biogenesis. Co-immunoprecipitation, RNase treatment, siRNA knockdown, immunofluorescence/nucleolar fractionation Journal of Biological Chemistry Medium 18420587
2008 NPM1/B23 binds SENP3 and SENP5 SUMO proteases in Xenopus egg extracts and is essential for stable accumulation of SENP3 and SENP5 in mammalian cells. Depletion of NPM1 or co-depletion of SENP3/SENP5 causes accumulation of SUMO proteins within nucleoli and defects in ribosome biogenesis similar to NPM1 loss. Co-immunoprecipitation (Xenopus extracts), siRNA depletion, SUMO immunofluorescence, ribosome biogenesis assay Journal of Cell Biology High 19015314
2006 A conserved GSGP loop motif in the NPM1 oligomerization domain (residues L102, G105, G107) is essential for ARF binding in vivo. Mutation of these core residues prevents ARF interaction, destabilizes NPM1 through increased ubiquitination and proteasomal degradation, impairs oligomerization, and delocalizes NPM1 from nucleolus to nucleoplasm. Site-directed mutagenesis, co-immunoprecipitation, ubiquitination assay, immunofluorescence, proteasome inhibitor treatment Journal of Biological Chemistry High 16679321
2005 DNA damage disrupts the ARF–NPM1(B23) interaction, triggers transient p53-independent translocation of ARF from nucleolus to nucleoplasm, and correlates with appearance of ARF–HDM2 complexes. By 24 h post-irradiation, NPM1–ARF interactions are restored. Immunofluorescence, co-immunoprecipitation, UV/IR irradiation time-course Cancer research Medium 16267006
2008 Nuclear Akt forms a complex with NPM1/B23 upon growth factor stimulation, with the C-terminus of NPM1 (residues 239–294) binding the Akt PH domain. Akt binding protects NPM1 from caspase-3-mediated proteolytic cleavage, thereby promoting cell survival. Akt2, but not other isoforms, specifically regulates NPM1 sumoylation and protein stability. Unsumoylated NPM1 (K263R) interacts strongly with Akt in the nucleoplasm even without growth factors. Co-immunoprecipitation, deletion mapping, caspase-3 cleavage assay, isoform-specific knockdown, cell survival assay Proceedings of the National Academy of Sciences High 18931307
2004 NPM3 interacts directly with NPM1/B23; co-immunoprecipitation shows the complex is resistant to RNase and high salt. The N-terminal residues 35–90 of B23 are required for their interaction. Overexpression of NPM3 decreases pre-rRNA synthesis and processing, while NPM3 mutants that cannot interact with B23 do not alter rRNA biogenesis. Yeast two-hybrid, co-immunoprecipitation, deletion mapping, pre-rRNA synthesis/processing assay, NPM3 mutant expression Journal of Biological Chemistry High 15596447
2010 Polo-like kinase 2 (Plk2) phosphorylates NPM1/B23 on serine 4 in vivo during S-phase in a Polo-box-dependent manner. Expression of a non-phosphorylatable NPM1 S4A mutant interferes with centriole reduplication in S-phase-arrested cells and causes dilution of centriole numbers in unperturbed cells, while phospho-mimicking mutants cause centriole accumulation. In vitro kinase assay, in vivo phosphorylation (Plk2/NPM1 interaction confirmed by Polo-box pull-down and co-IP), S4A/S4D mutant expression, centriole counting assay PLoS ONE High 20352051
2021 SIRT7 deacetylates NPM1 upon UV irradiation; deacetylation is required for stress-dependent relocation of NPM1 from nucleolus to nucleoplasm and subsequent binding to MDM2, thereby preventing p53 ubiquitination and degradation. SIRT7 catalytic activity is increased by ATR-mediated phosphorylation upon UV irradiation. In SIRT7-deficient cells, stress-dependent p53 stabilization is abrogated both in vitro and in vivo. Deacetylation assay, co-immunoprecipitation, immunofluorescence localization, ATR kinase assay, SIRT7 knockout mouse model, p53 ubiquitination assay Proceedings of the National Academy of Sciences High 33495326
2009 NPM1/B23 directly binds p21WAF1/CIP1; interaction confirmed by reciprocal co-immunoprecipitation and GST pull-down. NPM1 overexpression prolongs p21 half-life and inhibits its ubiquitination; NPM1 knockdown reduces p21 levels and enhances ubiquitination, establishing NPM1 as a positive post-translational stabilizer of p21. Reciprocal co-immunoprecipitation, GST pull-down, confocal colocalization, cycloheximide chase (half-life), ubiquitination assay, siRNA knockdown Cell Cycle High 19221506
2007 NPM1/B23 directly interacts with PES1 (pescadillo homolog); in vivo interaction confirmed by co-immunoprecipitation of endogenous proteins and in vitro by pull-down with mapped interaction domains. Knockdown of B23 by RNAi increases nucleoplasmic distribution of PES1, implicating NPM1 as a nucleolar targeting hub for PES1. Co-immunoprecipitation (endogenous), in vitro pull-down (domain mapping), siRNA knockdown, immunofluorescence Acta Biochimica et Biophysica Sinica Medium 20011973
2007 NPM1/B23 forms a complex with Ebp1 isoforms in a SUMOylation-dependent manner: p48 constitutively binds NPM1 in the nucleolus requiring K263 SUMOylation on NPM1, while p42 selectively binds unsumoylated NPM1 upon EGF stimulation requiring Ser360 phosphorylation on p42. NPM1 K263R (unsumoylated) triggers p42 nuclear translocation and abolishes p48 nucleolar residency. Knockdown of B23 substantially decreases ribosome biogenesis and cell survival. Co-immunoprecipitation, site-directed mutagenesis (NPM1 K263R; p42 S360A), confocal microscopy, ribosome biogenesis assay, siRNA knockdown Journal of Biological Chemistry High 17951246
2014 AKT phosphorylation of NPM1 at Ser48 prevents NPM1 oligomerization, resulting in nucleoplasmic retention of ARF and constitutive MDM2 inhibition that stabilizes p53. In contrast, oligomeric NPM1 drives nucleolar accumulation of ARF, which antagonizes the inhibitory ARF–MDM2 complex. The AKT inhibitor MK-2206 promotes ARF nucleolar localization and reduces mutant p53 stability in a xenograft pancreatic cancer model. Co-immunoprecipitation, phospho-specific antibody, AKT inhibitor treatment, in vivo xenograft model, immunofluorescence Oncotarget Medium 25071014
2018 Loss of NPM1 mutant (NPM1c) from the cytoplasm—either by nuclear relocalization via XPO1 inhibition or by targeted degradation—results in immediate downregulation of HOX genes followed by AML cell differentiation, establishing that NPM1c is required to maintain the leukemic state through HOX gene expression. Targeted protein degradation (degron system), XPO1 inhibitor treatment, gene expression analysis (RNA-seq), mouse leukemia survival model Cancer Cell High 30205049
2023 Mutant NPM1 (NPM1c) directly binds to specific chromatin targets co-occupied by histone methyltransferase KMT2A/MLL1. Targeted degradation of NPM1c leads to rapid decrease in gene expression and loss of RNA Pol II and activating histone modifications at its target loci (including HOXA/B and MEIS1), establishing NPM1c as a direct transcriptional driver cooperating with MLL1. ChIP-seq, CUT&RUN, targeted protein degradation, RNA-seq, co-occupancy analysis Cancer Discovery High 36455613
2023 NPM1c binds a subset of active gene promoters in NPM1c AMLs (including HOXA/B cluster genes and MEIS1), sustains their active transcription by orchestrating a transcription hub, and maintains active chromatin landscape by inhibiting histone deacetylase activity. ChIP-seq, CUT&RUN, ATAC-seq, HDAC activity assay, RNA-seq Cancer Discovery High 36455589
2024 Oligomeric NPM1 recruits histone demethylase KDM5b to the TSC1 gene promoter, reducing H3K4me3 modification and repressing TSC1 expression, thereby facilitating mTOR-dependent inflammatory glycolysis in macrophages and antagonizing their reparative function after myocardial infarction. Co-immunoprecipitation, ChIP-qPCR, macrophage-specific NPM1 knockout mouse, metabolite profiling, RNA-seq, antisense oligonucleotide treatment Circulation High 38390737
2024 NPM1 associates with transcription factor IRF1 and sequesters it from binding to Nlrc5 and Ciita gene promoters, thereby suppressing IRF1-mediated expression of MHC-I and MHC-II molecules in tumor cells and promoting immune evasion. Co-immunoprecipitation (NPM1–IRF1), dual-luciferase reporter assay, ChIP-qPCR, NPM1 knockout, flow cytometry (MHC-I/II), T-cell killing assay Journal of Hematology & Oncology High 39402629
1997 YY1 transcription factor binds to the NPM1 gene promoter at the -371/-344 nt footprint region (within the -741/-250 nt enhancer fragment), as established by EMSA gel-shift and DNA footprinting, implicating YY1 in regulation of NPM1 gene expression. EMSA, DNA footprinting, nuclear extract competition assay Nucleic Acids Research Medium 9092633
2005 NPM1/B23 regulates PCNA expression through YY1: NPM1 overexpression upregulates YY1 and PCNA, while NPM1 siRNA reduces both. ChIP assay shows YY1 binding to the PCNA promoter initiation site with H4 acetylation; this binding is diminished in NPM1-depleted cells. Mutation of the YY1 binding site abolishes PCNA promoter activity. siRNA knockdown, ChIP assay, luciferase reporter assay (YY1 binding site mutation), Western blot Biochemical and Biophysical Research Communications Medium 16099430
2008 NPM-ALK fusion protein oncogenically induces CD274 (PD-L1) expression through STAT3. STAT3 binds the CD274 gene promoter in vitro (EMSA) and in vivo (ChIP). STAT3 is required for PD-L1 expression (siRNA depletion). CD274 induction requires kinase-active NPM/ALK (abrogated by K210R kinase-dead mutant and small-molecule ALK inhibitor). EMSA, ChIP, siRNA knockdown, kinase-inactive mutant (K210R), small-molecule ALK inhibitor, RT-PCR/Western Proceedings of the National Academy of Sciences High 19088198
1994 MNDA binds NPM1/B23 in vitro and by co-immunoprecipitation. The binding requires NPM residues 117–175 (containing a nuclear localization signal and acidic clusters), as NPM-ALK (residues 1–117) does not bind MNDA, but NPM-MLF1 (residues 1–175) does. In vitro binding assay, co-immunoprecipitation, deletion comparison using fusion protein chimeras Experimental Hematology Medium 9328447
2007 NPM/ALK interacts with and phosphorylates PSF (polypyrimidine tract binding protein-associated splicing factor) at Tyr293. PSF is a direct substrate of purified ALK kinase domain in vitro. Y293F PSF is not phosphorylated and is not delocalized in NPM/ALK+ cells. PSF phosphorylation increases its RNA binding and decreases PSF-mediated suppression of GAGE6 expression. Forced PSF overexpression inhibits proliferation and induces apoptosis in NPM/ALK+ cells. Proteomic co-IP (mass spectrometry), in vitro kinase assay with purified ALK domain, site-directed mutagenesis (Y293F), immunofluorescence, RNA binding assay Blood High 17537995
2006 SHP1 tyrosine phosphatase directly dephosphorylates NPM-ALK; pull-down and co-IP demonstrate SHP1/NPM-ALK association in cytoplasmic bodies containing Y664-phosphorylated NPM-ALK. SHP1 RNAi leads to NPM-ALK hyperphosphorylation, STAT3 activation, and increased proliferation. SHP1 overexpression in NPM-ALK+ 3T3 cells decreases NPM-ALK phosphorylation and tumor growth in nude mice. Pull-down, co-immunoprecipitation, confocal microscopy, in vitro dephosphorylation assay, RNAi, tumor xenograft Blood High 16469875
1992 NPM1/B23 translocation (redistribution from nucleolus to nucleoplasm) induced by camptothecin is a reversible process: upon drug removal, NPM1 relocalizes to nucleoli within 2 h even in the presence of cycloheximide (blocking new protein synthesis), indicating redistribution of existing protein rather than synthesis of new protein. There is no significant change in NPM1 phosphorylation state or oligomeric cross-linkage during drug treatment. Immunofluorescence/immunocytochemistry, Western blot (phosphorylation), cross-linking analysis, cycloheximide chase, drug washout experiment Experimental Cell Research Medium 1426041
1995 NPM1/B23 exists predominantly as an oligomer (~95% of total NPM in HeLa cells). The oligomer sediments faster than monomer in sucrose gradients and is resistant to DNase, RNase, 10 mM EDTA, 1 M NaCl, and lyophilization, but is reversibly dissociated by 3 M urea. Native PAGE Western blot, sucrose density gradient centrifugation, chemical treatments, crosslinking Biochimica et Biophysica Acta Medium 7772597
2016 P-STAT5 (phosphorylated at Y694) diminishes NPM1 expression by impairing BRCA1-BARD1 ubiquitin ligase activity, which normally controls NPM1 stability. Decreased NPM1 leads to reduced p53 levels and enhanced cell survival. Conversely, NPM1 negatively regulates STAT5 phosphorylation and preserves unphosphorylated STAT5 protein levels. Co-immunoprecipitation, siRNA knockdown, Western blot (protein stability), STAT5 phosphorylation assay Cell Death & Disease Medium 28005077

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proceedings of the National Academy of Sciences of the United States of America 624 19088198
2000 Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell 561 11051553
2023 The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature 411 36922593
2004 Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Molecular and cellular biology 328 14729947
1997 Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. Molecular and cellular biology 314 9121481
2018 Mutant NPM1 Maintains the Leukemic State through HOX Expression. Cancer cell 266 30205049
2020 NPM1-mutated acute myeloid leukemia: from bench to bedside. Blood 263 32609823
2010 NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling. Biochemistry research international 250 21152184
1999 Nucleolar protein B23 has molecular chaperone activities. Protein science : a publication of the Protein Society 208 10211837
2010 Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 197 21030560
2007 The structure and functions of NPM1/Nucleophsmin/B23, a multifunctional nucleolar acidic protein. Journal of biochemistry 175 18024471
2007 Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias. Haematologica 156 17488663
2000 Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 156 10994999
2017 Biological and clinical consequences of NPM1 mutations in AML. Leukemia 152 28111462
2005 Cell line OCI/AML3 bears exon-12 NPM gene mutation-A and cytoplasmic expression of nucleophosmin. Leukemia 137 16079892
2004 ARF impedes NPM/B23 shuttling in an Mdm2-sensitive tumor suppressor pathway. Molecular and cellular biology 136 15485902
1996 Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa. The Journal of pathology 130 8778315
2023 Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia. Cancer discovery 113 36455613
2019 Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation. Nature communications 105 31048683
2005 DNA damage disrupts the p14ARF-B23(nucleophosmin) interaction and triggers a transient subnuclear redistribution of p14ARF. Cancer research 105 16267006
2008 Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse. Blood 101 18212245
2008 Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation. The Journal of biological chemistry 101 18420587
2008 Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases. The Journal of cell biology 95 19015314
2002 Resistance to UV-induced cell-killing in nucleophosmin/B23 over-expressed NIH 3T3 fibroblasts: enhancement of DNA repair and up-regulation of PCNA in association with nucleophosmin/B23 over-expression. Carcinogenesis 90 11756229
2023 Mutant NPM1 Hijacks Transcriptional Hubs to Maintain Pathogenic Gene Programs in Acute Myeloid Leukemia. Cancer discovery 83 36455589
2020 CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer. Journal of cellular and molecular medicine 79 32378344
2017 When the good go bad: Mutant NPM1 in acute myeloid leukemia. Blood reviews 75 29157973
2004 Protein NPM3 interacts with the multifunctional nucleolar protein B23/nucleophosmin and inhibits ribosome biogenesis. The Journal of biological chemistry 73 15596447
2024 Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML. Blood 72 38691678
2018 NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse. Blood advances 70 30455361
2008 Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival. Proceedings of the National Academy of Sciences of the United States of America 67 18931307
1992 Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with selected cytotoxic agents (studies of B23-translocation mechanism). Experimental cell research 66 1426041
2021 How I diagnose and treat NPM1-mutated AML. Blood 64 33171486
2019 Clinicopathologic and genetic characterization of nonacute NPM1-mutated myeloid neoplasms. Blood advances 63 31085507
2024 Targeting NPM1 Epigenetically Promotes Postinfarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism. Circulation 60 38390737
2015 Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation. Nature communications 60 25600590
2012 Expression of nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells. Journal of biomedical science 60 22631075
2006 Essential role of the B23/NPM core domain in regulating ARF binding and B23 stability. The Journal of biological chemistry 55 16679321
2006 DNA damage, p14ARF, nucleophosmin (NPM/B23), and cancer. Journal of molecular histology 55 16855788
1990 Structure of the gene for rat nucleolar protein B23. The Journal of biological chemistry 55 2211699
2021 The potential role of nucleophosmin (NPM1) in the development of cancer. Journal of cellular physiology 53 33959979
2005 Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis. Cancer biology & therapy 53 16103750
2021 SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress. Proceedings of the National Academy of Sciences of the United States of America 52 33495326
2007 Ebp1 association with nucleophosmin/B23 is essential for regulating cell proliferation and suppressing apoptosis. The Journal of biological chemistry 51 17951246
1995 Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. Biochimica et biophysica acta 51 7772597
2015 IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia. Cancer research 49 25795706
2017 Coexisting and cooperating mutations in NPM1-mutated acute myeloid leukemia. Leukemia research 48 28152414
2006 A "liaison dangereuse" between AUF1/hnRNPD and the oncogenic tyrosine kinase NPM-ALK. Blood 45 16835382
2015 Chronic myelomonocytic leukemia with nucleophosmin (NPM1) mutation. European journal of haematology 43 25809997
2015 NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape. Scientific reports 42 26559910
2011 IL-2R common gamma-chain is epigenetically silenced by nucleophosphin-anaplastic lymphoma kinase (NPM-ALK) and acts as a tumor suppressor by targeting NPM-ALK. Proceedings of the National Academy of Sciences of the United States of America 42 21715655
2006 B23 and ARF: friends or foes? Cell biochemistry and biophysics 42 16943625
1997 Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region. Nucleic acids research 42 9092633
2006 SHP1 tyrosine phosphatase negatively regulates NPM-ALK tyrosine kinase signaling. Blood 41 16469875
1996 PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia. Haematologica 41 8952164
2022 Targeted therapy in NPM1-mutated AML: Knowns and unknowns. Frontiers in oncology 38 36237321
2017 NPM1 Mutant Mediated PML Delocalization and Stabilization Enhances Autophagy and Cell Survival in Leukemic Cells. Theranostics 38 28740552
1995 Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma. British journal of haematology 37 7772531
2021 Significance of NPM1 Gene Mutations in AML. International journal of molecular sciences 36 34576201
2009 NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner. Blood 36 19286999
2025 Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35 40504618
2020 IL10RA modulates crizotinib sensitivity in NPM1-ALK+ anaplastic large cell lymphoma. Blood 35 32573700
2018 Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival. Theranostics 35 30214626
2021 Biological and therapeutic implications of a unique subtype of NPM1 mutated AML. Nature communications 34 33594052
2020 Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia. Therapeutic advances in hematology 34 32071709
2011 Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP. Nucleic acids research 34 21705779
2010 Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PloS one 34 20352051
2007 Oncogenic role of nucleophosmin/B23. Chang Gung medical journal 34 17939258
2009 Nucleophosmin/B23 interacts with p21WAF1/CIP1 and contributes to its stability. Cell cycle (Georgetown, Tex.) 33 19221506
2007 NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma. Blood 33 17537995
2023 NPM 1 Mutations in AML-The Landscape in 2023. Cancers 31 36831522
2024 Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML. Blood cancer discovery 30 37917833
2014 AKT regulates NPM dependent ARF localization and p53mut stability in tumors. Oncotarget 30 25071014
2010 Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA. Oncogene 30 21102525
2019 LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1. Scientific reports 28 31406141
2011 Oncogenic tyrosine kinase NPM-ALK induces expression of the growth-promoting receptor ICOS. Blood 28 21765024
2006 Loss of the NPM1 gene in myeloid disorders with chromosome 5 rearrangements. Leukemia 28 16341035
2024 NPM1 inhibits tumoral antigen presentation to promote immune evasion and tumor progression. Journal of hematology & oncology 27 39402629
2016 Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2. Cell death & disease 27 28005077
2016 Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice. Blood 26 26747246
2013 NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism. The Journal of pathology 25 23338972
2007 Relationship between adenovirus DNA replication proteins and nucleolar proteins B23.1 and B23.2. The Journal of general virology 25 18024892
2024 Functions of the native NPM1 protein and its leukemic mutant. Leukemia 23 39690184
2020 Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid. Virulence 23 33073687
2024 AURKA inhibition induces Ewing's sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis. Cell death & disease 21 38287009
2023 Cytoplasmic Expression of TP53INP2 Modulated by Demethylase FTO and Mutant NPM1 Promotes Autophagy in Leukemia Cells. International journal of molecular sciences 21 36675134
2012 Estrogen stimulates the proliferation of human endometrial cancer cells by stabilizing nucleophosmin/B23 (NPM/B23). Journal of molecular medicine (Berlin, Germany) 21 22926011
2021 NPM-ALK: A Driver of Lymphoma Pathogenesis and a Therapeutic Target. Cancers 20 33466277
2018 INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia. Journal of experimental & clinical cancer research : CR 20 29343273
2016 NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma. Oncogene 19 27694894
2015 Insights into the regulation of neuronal viability by nucleophosmin/B23. Experimental biology and medicine (Maywood, N.J.) 19 25908633
2005 Nucleophosmin/B23 regulates PCNA promoter through YY1. Biochemical and biophysical research communications 19 16099430
2019 Implication of B23/NPM1 in Viral Infections, Potential Uses of B23/NPM1 Inhibitors as Antiviral Therapy. Infectious disorders drug targets 18 29589547
1997 MNDA binds NPM/B23 and the NPM-MLF1 chimera generated by the t(3;5) associated with myelodysplastic syndrome and acute myeloid leukemia. Experimental hematology 18 9328447
2015 Involvement of Nucleophosmin (NPM1/B23) in Assembly of Infectious HPV16 Capsids. Papillomavirus research (Amsterdam, Netherlands) 17 27398412
2022 Cell origin-dependent cooperativity of mutant Dnmt3a and Npm1 in clonal hematopoiesis and myeloid malignancy. Blood advances 16 35413095
2017 Nucleophosmin (NPM1)/B23 in the Proteome of Human Astrocytic Cells Restricts Chikungunya Virus Replication. Journal of proteome research 16 28959884
2018 Characterization and diagnostic application of genomic NPM-ALK fusion sequences in anaplastic large-cell lymphoma. Oncotarget 15 29899875
2009 B23 interacts with PES1 and is involved in nucleolar localization of PES1. Acta biochimica et biophysica Sinica 15 20011973
1996 Detection of the NPM-ALK genomic rearrangement of Ki-1 lymphoma and isolation of the involved NPM and ALK introns. Diagnostic molecular pathology : the American journal of surgical pathology, part B 15 8866227

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