Affinage

NSD3

Histone-lysine N-methyltransferase NSD3 · UniProt Q9BZ95

Length
1437 aa
Mass
161.6 kDa
Annotated
2026-04-29
79 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NSD3 is a histone lysine methyltransferase that deposits H3K36me1/me2 at active promoters and enhancers to regulate transcription, cell cycle progression, and developmental programs, while also functioning through a catalytically inactive short isoform (NSD3S) that serves as a chromatin adaptor bridging BRD4, CHD8, and MYC (PMID:39390582, PMID:26626481, PMID:21555454). The long isoform catalyzes H3K36 methylation through its SET domain—regulated by an autoinhibitory loop relieved by the oncogenic T1232A variant—and also methylates non-histone substrates IRF3 (K366) and EGFR (K721) to modulate innate immune signaling and receptor tyrosine kinase activity, respectively (PMID:33536620, PMID:29101251, PMID:28102297). NSD3 promotes sister chromatid cohesion by recruiting the kollerin cohesin-loader complex at mitotic exit, and the NSD3S isoform protects stalled replication forks from MRE11-mediated degradation downstream of ATR kinase, conferring PARP inhibitor resistance (PMID:37288770, PMID:40578344). NSD3 is recurrently amplified or mutationally activated in breast cancer, lung squamous cell carcinoma, and acute myeloid leukemia, and NSD3-NUT fusions drive NUT midline carcinoma (PMID:33536620, PMID:24875858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 Medium

    Identification of NSD3 as a SET-domain gene at 8p11.2 with two major isoforms (long/catalytic and short/PWWP-only) established the molecular framework for understanding its dual enzymatic and adaptor functions.

    Evidence cDNA cloning, domain analysis, and FISH mapping in breast cancer amplicon

    PMID:11549311

    Open questions at the time
    • No enzymatic activity demonstrated
    • Protein partners unknown
    • Single-lab characterization
  2. 2006 Medium

    Demonstration that the WHISTLE isoform possesses HMTase activity dependent on the SET domain C297 residue and PWWP region, and that this activity is required for transcriptional repression and apoptosis induction, established NSD3 as a functional methyltransferase.

    Evidence Point mutagenesis, luciferase reporter, caspase-3 assay

    PMID:17239852

    Open questions at the time
    • Histone substrate specificity not defined
    • No structural basis for catalysis
    • Single-lab study
  3. 2011 High

    Discovery that NSD3 physically interacts with BRD4 via the ET domain and deposits H3K36me at BRD4-target genes revealed how NSD3 is genomically targeted and established the BRD4-NSD3 axis as a transcriptional activation mechanism independent of pTEFb.

    Evidence Mass spectrometry pulldown, reciprocal Co-IP, ChIP, siRNA knockdown in human cells

    PMID:21555454

    Open questions at the time
    • Isoform-specific contributions to BRD4 complex not resolved
    • Genome-wide H3K36me targets not mapped
    • Mechanism of pTEFb-independent activation unclear
  4. 2012 High

    Structural determination of the PHD5-C5HCH module revealed a novel integrated reader that binds H3K4me0/H3K9me3, providing a chromatin-targeting mechanism distinct from NSD1 and NSD2.

    Evidence X-ray crystallography of PHD5-C5HCH with H3 peptide complexes and binding assays

    PMID:23269674

    Open questions at the time
    • Genomic loci where PHD5-dependent targeting operates not identified
    • Functional consequence of H3K9me3 recognition on gene expression not tested
  5. 2014 High

    Two studies established NSD3's biological roles in differentiation: NSD3-NUT fusions block differentiation in NUT midline carcinoma through BRD4, and NSD3 is required for neural crest specification/migration via H3K36me2 at the Sox10 locus, demonstrating context-dependent developmental and oncogenic functions.

    Evidence shRNA/overexpression in NMC cells with BET inhibitor validation; morpholino and dominant-negative in chick embryos with ChIP

    PMID:24875858 PMID:25318671

    Open questions at the time
    • Direct NSD3-NUT catalytic activity not assessed
    • Full target gene repertoire in neural crest unknown
  6. 2015 High

    Identification of NSD3-short as a non-catalytic adaptor bridging BRD4 to CHD8 at super-enhancers in AML cells resolved how the short isoform contributes to oncogenesis independently of methyltransferase activity.

    Evidence Co-IP, ChIP-seq, CRISPR/shRNA knockdown in AML cells with transcriptional and phenotypic readouts

    PMID:26626481

    Open questions at the time
    • Whether NSD3S-CHD8 complex remodels nucleosomes directly not shown
    • Relative contribution of long vs. short isoform in AML unclear
  7. 2016 High

    Crystal structure of the BRD4 ET–NSD3 peptide interface and demonstration that NSD3 catalytic activity drives G1-to-S cell cycle progression through H3K36me2 at CDC6/CDK2 gene bodies defined both the structural basis of the BRD4 interaction and a direct proliferative mechanism.

    Evidence X-ray crystallography with structure-guided mutagenesis; ChIP with catalytic mutant rescue and cell cycle analysis in HNSCC cells

    PMID:27285764 PMID:27291650

    Open questions at the time
    • Whether cell cycle role is BRD4-dependent not tested
    • Genome-wide targets beyond CDC6/CDK2 not mapped
  8. 2017 High

    Discovery that NSD3 methylates non-histone substrates IRF3 (K366) and EGFR (K721) expanded NSD3's substrate repertoire beyond histones, linking it to innate immune signaling and receptor tyrosine kinase pathways.

    Evidence In vitro methylation assays, Co-IP, NSD3 KO mice for IRF3; siRNA and cell cycle analysis for EGFR in HNSCC

    PMID:28102297 PMID:29101251

    Open questions at the time
    • Full non-histone substrate repertoire unknown
    • Structural basis for non-histone substrate recognition not determined
    • In vivo relevance of EGFR K721me not demonstrated in animal models
  9. 2019 High

    Development of the PWWP1-domain chemical probe BI-9321 that downregulates MYC in AML provided pharmacological validation that the PWWP1 reader domain is essential for NSD3-dependent oncogenic transcription.

    Evidence Fragment-based drug discovery, structural characterization, cellular target engagement in AML cells

    PMID:31285596

    Open questions at the time
    • Selectivity over NSD1/NSD2 PWWP domains not fully defined
    • In vivo anti-tumor efficacy not demonstrated
  10. 2021 High

    Identification of NSD3 T1232A as a gain-of-function driver in lung squamous cell carcinoma that relieves autoinhibition to increase H3K36me2, and development of NSD3-targeting PROTACs, defined NSD3 as a druggable oncogenic target with a precise structural mechanism of activation.

    Evidence In vitro methyltransferase assay, structural dynamic analysis, LUSC mouse models, PDX; PROTAC degradation with RNA-seq comparison to CRISPR KO

    PMID:33536620 PMID:34469831

    Open questions at the time
    • Whether autoinhibition relief mechanism is generalizable to other NSD3 mutations not tested
    • Clinical applicability of NSD3 PROTACs not evaluated
  11. 2023 High

    Discovery that NSD3 interacts with the kollerin cohesin loader to promote sister chromatid cohesion at mitotic exit revealed a novel non-transcriptional, cell-division-coupled function for NSD3's catalytic activity.

    Evidence Co-IP, chromatin fractionation, live cell imaging, catalytic mutant rescue

    PMID:37288770

    Open questions at the time
    • Histone mark deposited at cohesion sites not identified
    • Whether cohesion defects contribute to NSD3-driven aneuploidy/oncogenesis not established
  12. 2024 High

    Genome-wide dissection of H3K36me2 deposition showed NSD3 uniquely marks active promoters and enhancers rather than broad intergenic domains, establishing a distinct chromatin niche from NSD1/NSD2 and clarifying the non-redundant function of NSD3 in the NSD family.

    Evidence Sequential CRISPR knockouts of K36 methyltransferases with ChIP-seq in mouse mesenchymal stem cells

    PMID:39390582

    Open questions at the time
    • Whether promoter-specific targeting depends on reader domains or interacting partners not resolved
    • Functional consequence of promoter-restricted H3K36me2 vs. intergenic domains not tested
  13. 2025 High

    Demonstration that NSD3S is recruited to stalled replication forks by ATR kinase to protect nascent DNA from MRE11-mediated degradation, conferring PARP inhibitor resistance, revealed a replication stress response function for the catalytically inactive isoform.

    Evidence Co-IP, proximity ligation, fork protection assay, NSD3-targeting PROTAC, xenograft and PDX models

    PMID:40578344

    Open questions at the time
    • Phosphorylation site(s) on NSD3S mediating ATR-dependent recruitment not mapped
    • Whether NSD3S fork protection is PWWP1-dependent not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how NSD3's promoter/enhancer-specific H3K36me2 deposition is mechanistically directed, the full scope of non-histone substrates, the structural basis for autoinhibition and its relief, and whether the cohesion and replication fork protection functions of NSD3 are coordinated or independent.
  • No full-length NSD3 structure available
  • Relative contributions of long and short isoforms in specific cancer types remain unclear
  • Interplay between NSD3 reader domains and catalytic activity in genomic targeting not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0060090 molecular adaptor activity 3 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 6 GO:0005694 chromosome 3
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
BRD4CHD8EGFRG9AIRF3MAU2MYCNIPBL
Complex memberships
BRD4-NSD3-CHD8NSD3-kollerin (NIPBL/MAU2)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 NSD3 interacts with the extraterminal (ET) domain of BRD4 (and BRD2/BRD3), and the BRD4/NSD3 complex regulates H3K36 methylation at BRD4 target genes; NSD3 is recruited to regulated genes in a BRD4-dependent manner and imparts pTEFb-independent transcriptional activation. Proteomic/mass spectrometry pulldown, co-immunoprecipitation, ChIP, siRNA knockdown with H3K36me measurement Molecular and cellular biology High 21555454
2015 NSD3-short (a short isoform lacking the methyltransferase domain) acts as an adaptor protein linking BRD4 to the CHD8 chromatin remodeler via its PWWP chromatin-reader module and an acidic transactivation domain; the BRD4-NSD3-CHD8 complex co-localizes at super-enhancers in AML cells and is required for leukemia maintenance. Co-immunoprecipitation, ChIP-seq, CRISPR/shRNA knockdown with transcriptional and phenotypic readouts, genetic epistasis Molecular cell High 26626481
2016 Crystal structure of the BRD4 ET domain bound to an NSD3-derived amphipathic peptide revealed that ET domain recognition occurs via a two-strand antiparallel β-sheet anchored on a hydrophobic cleft of a three-helix bundle; this structural mechanism is essential for AML maintenance. X-ray crystallography, structure-guided mutagenesis, functional validation in AML cells Structure (London, England : 1993) High 27291650
2012 The PHD5-C5HCH module of NSD3 folds into a novel integrated PHD-PHD-like structural module that binds unmodified H3K4 and trimethylated H3K9 (H3K9me3) on the surface of PHD5; this differs from NSD2 (which prefers H3K9me0) and NSD1 (which does not bind H3 peptides), providing a mechanism for genomic targeting. X-ray crystallography of PHD5-C5HCH free and in complex with H3 peptides; binding assays The Journal of biological chemistry High 23269674
2021 NSD3 is the principal oncogenic driver in lung squamous cell carcinoma (LUSC) within the 8p11-12 amplicon; a cancer-associated variant NSD3(T1232A) shows increased catalytic activity for H3K36me2 in vitro and in vivo, and structural dynamic analyses revealed that T1232A relieves auto-inhibition and increases H3 substrate accessibility. In vitro methyltransferase assay, structural dynamic analysis, mouse LUSC model (KO and knock-in), patient-derived xenografts, ChIP-seq Nature High 33536620
2017 NSD3 (WHSC1L1) directly methylates IRF3 at lysine 366 (K366me1) via its SET domain; NSD3 binds the IRF3 C-terminal region through its PWWP1 domain. K366 monomethylation promotes IRF3 dissociation from the phosphatase PP1cc, sustaining IRF3 phosphorylation and type I interferon production during antiviral innate immunity. Mass spectrometry identification of IRF3-associated proteins, co-immunoprecipitation, in vitro methylation assay, NSD3 knockout mice, site-directed mutagenesis The Journal of experimental medicine High 29101251
2017 WHSC1L1 (NSD3) mono-methylates EGFR at lysine 721 (K721) in the tyrosine kinase domain, enhancing ERK cascade activation without EGF stimulation; nuclear EGFR K721 methylation also enhances interaction with PCNA, promoting DNA synthesis and cell cycle progression in head and neck squamous cell carcinoma. In vitro methylation assay, co-immunoprecipitation, functional siRNA knockdown, cell cycle analysis Scientific reports High 28102297
2016 WHSC1L1 (NSD3) and H3K36me2 are enriched in the gene bodies of CDC6 and CDK2; WHSC1L1 knockdown causes G0/G1 arrest that is rescued by wild-type WHSC1L1 but not by enzyme-inactive WHSC1L1, demonstrating that catalytic activity-dependent H3K36me2 drives G1-to-S phase transition in head and neck cancer cells. ChIP, siRNA knockdown, cell cycle analysis, rescue with catalytic mutant Oncotarget High 27285764
2020 The long isoform of NSD3 (but not the short isoform lacking the catalytic domain) cooperates with EZH2 and RNA polymerase II to stimulate H3K36me2/3-dependent transactivation of genes involved in NOTCH receptor cleavage, leading to nuclear accumulation of NICD and NICD-mediated E-cadherin repression in breast cancer. Co-immunoprecipitation, ChIP, isoform-specific knockdown/overexpression, in vivo mouse model Cancer research High 32967925
2019 The PWWP1 domain of NSD3 binds the methyl-lysine site and is required for viability of AML cells; the fragment-derived chemical probe BI-9321 antagonizes this domain with sub-micromolar in vitro activity and cellular target engagement, downregulating Myc mRNA. Fragment-based drug discovery, structural characterization, cellular target engagement assay, mRNA expression Nature chemical biology High 31285596
2014 NSD3-NUT fusion oncoprotein is necessary and sufficient for blockade of differentiation and maintenance of proliferation in NUT midline carcinoma cells; NSD3-NUT binds BRD4, and NSD3 is also required for the blockade of differentiation in BRD4-NUT-expressing NMC cells. Patient-derived cell line, shRNA knockdown, overexpression, co-immunoprecipitation, BET bromodomain inhibitor treatment Cancer discovery High 24875858
2023 NSD3 (long isoform) interacts with the cohesin loader complex kollerin (NIPBL/MAU2) and promotes chromatin recruitment of MAU2 and cohesin at mitotic exit; NSD3 associates with chromatin in early anaphase before cohesin loading and its methyltransferase activity is required for efficient sister chromatid cohesion. Co-immunoprecipitation, chromatin fractionation, live cell imaging, siRNA knockdown, catalytic mutant rescue Journal of cell science High 37288770
2014 NSD3 is required for neural crest specification and migration in chick embryos; NSD3 loss impairs expression of neural plate border gene Msx1 and neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3; H3K36me2 at the Sox10 locus specifically requires NSD3, and NSD3-related methyltransferase activity is independently required for neural crest migration. Morpholino knockdown in chick, dominant-negative expression, ChIP for H3K36me2, temporal rescue experiments Molecular biology of the cell High 25318671
2024 NSD3 deposits H3K36me2 peaks specifically at active promoters and enhancers (not broad intergenic domains), occupying a distinct genomic niche from NSD1/NSD2 which establish broad intergenic H3K36me2 domains; a hierarchy of K36 methyltransferase activity was established: NSD1 > NSD2 > NSD3 > ASH1L. Sequential CRISPR knockouts of multiple K36 methyltransferases, ChIP-seq, comparative H3K36me1/2/3 mapping in mouse mesenchymal stem cells Genome biology High 39390582
2021 A NSD3-targeting PROTAC (MS9715) linking BI-9321 (PWWP1 antagonist) to a VHL ligand induces specific NSD3 degradation and suppresses both NSD3- and cMyc-associated gene expression programs in hematological cancer cells; degradation is superior to PWWP1 domain blockade alone. PROTAC design, Western blot protein degradation, RNA-seq, CRISPR-Cas9 NSD3 KO comparison, cell viability Cell chemical biology High 34469831
2010 NSD3 (WHISTLE isoform) is recruited to the p450c17 promoter via interaction with SF-1 and represses steroidogenesis gene transcription during prepubertal stages; it interacts with HSP90α and the H3K9 demethylase JMJD1C, which subsequently replaces WHISTLE to activate target gene expression. TAP immunoaffinity purification of WHISTLE complexes, co-immunoprecipitation, ChIP Nucleic acids research Medium 20530532
2006 The WHISTLE isoform of NSD3 induces apoptosis in an HMTase activity-dependent manner and represses transcription through HDAC1 recruitment; the N-terminus PWWP region is required for HMTase activity, and SET domain cysteine 297 is a critical catalytic residue. Point mutagenesis, deletion mapping, luciferase reporter assay, caspase-3 activation assay Experimental cell research Medium 17239852
2025 NSD3 interacts with and methylates NSD3 itself at lysine 477 (via EHMT2); this methylation stabilizes NSD3 protein levels in variant hESCs by protecting it from proteasomal degradation, driving oncogenic transformation. Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis, protein stability assays, NSD3 knockdown rescue Life science alliance Medium 39741006
2018 NSD3-short (NSD3S) directly interacts with MYC; a TR-FRET assay was developed to monitor this interaction and confirmed by an orthogonal protein-protein interaction assay, supporting a mechanism by which NSD3S regulates cell proliferation through MYC engagement. TR-FRET cell lysate assay, orthogonal Co-IP/pulldown confirmation Assay and drug development technologies Medium 29634317
2024 NSD3 binds PPP1CB and p-STAT3, forming a trimeric complex that dephosphorylates p-STAT3 via PPP1CB phosphatase activity, leading to suppression of HK2 transcription and glycolysis inhibition in lung adenocarcinoma. Co-immunoprecipitation, siRNA knockdown, metabolic assays (glucose uptake, lactate), Western blot Advanced science Medium 39119928
2019 ISO-induced cardiac hypertrophy decreases NSD3 expression, which reduces H3K27me2/3 on the ANF promoter and disrupts NSD3-BRD4 association; overexpression of NSD3 attenuates hypertrophy by promoting BRD4-association and H3K27 methylation to suppress ANF transcription. Co-immunoprecipitation, ChIP, overexpression and knockdown in cardiomyocytes, in vivo mouse model FEBS letters Medium 31254363
2025 The short isoform NSD3S (lacking the methyltransferase domain) is stabilized by CUL3-ZBTB2 E3 ligase complex dysregulation; ATR kinase drives localization of NSD3S to stalled replication forks, where NSD3S antagonizes PTIP-dependent MRE11 nuclease recruitment to protect nascent DNA from degradation and confer PARP inhibitor resistance. Co-immunoprecipitation, proximity ligation, replication fork protection assay, NSD3-targeting PROTAC, xenograft and PDX mouse models Molecular cell High 40578344
2025 NSD3 specifically enhances H3K27 di-methylation (not H3K36me) in osteosarcoma cells to inactivate the transcriptional repressor ARID3A, causing altered expression of RUNX2, MMP13, OCT4, and NANOG and a shift toward a primitive differentiation state. CRISPR-Cas9 and lentiviral gain/loss-of-function, ChIP, transcriptomic analysis, spontaneous metastasis mouse model Cancer letters Medium 40967468
2023 WHSC1L1 (NSD3) epigenetically suppresses VMP1 transcription via H3K36me2-dependent recruitment of DNMT3A to the VMP1 promoter following HSV-1 infection; NSD3 upregulation impairs mitophagy and promotes neuroinflammation in microglia. ChIP, siRNA knockdown, VMP1 overexpression rescue, in vivo mouse HSV-1 infection model Molecular immunology Medium 37748280
2026 NSD3 is recruited to β-globin gene promoters by G9a; NSD3 stabilizes Mediator complex binding at the promoter and facilitates SETD2-mediated H3K36me3 in the gene body to activate globin gene expression; G9a, NSD3, and SETD2 form a coactivator axis in differentiating erythroid cells. Co-immunoprecipitation, ChIP, siRNA knockdown of NSD3 and G9a, gene expression analysis in differentiating erythroid cells Frontiers in cell and developmental biology Medium 41970952
2001 NSD3 (WHSC1L1) encodes a protein with two PWWP domains, five PHD zinc finger motifs, a SAC domain, and a SET domain; two major isoforms arise from alternative splicing — a long isoform (1437 aa, full SET domain) and a short isoform (645 aa, PWWP domain only); the gene maps to 8p11.2 and is frequently amplified in breast cancer. cDNA cloning, genomic mapping, domain analysis, Northern blot, FISH Genomics Medium 11549311

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Molecular and cellular biology 435 21555454
2014 NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. Cancer discovery 210 24875858
2019 WHISTLE: a high-accuracy map of the human N6-methyladenosine (m6A) epitranscriptome predicted using a machine learning approach. Nucleic acids research 178 30993345
2002 NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with t(8;11)(p11.2;p15). Blood 152 11986249
2001 NSD3, a new SET domain-containing gene, maps to 8p12 and is amplified in human breast cancer cell lines. Genomics 138 11374904
2015 NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler. Molecular cell 131 26626481
2021 Elevated NSD3 histone methylation activity drives squamous cell lung cancer. Nature 127 33536620
2019 Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nature chemical biology 75 31285596
2010 Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance. Nucleic acids research 67 20530532
2007 Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations. International journal of andrology 66 17705804
2020 NSD3-Induced Methylation of H3K36 Activates NOTCH Signaling to Drive Breast Tumor Initiation and Metastatic Progression. Cancer research 63 32967925
2016 Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4. Structure (London, England : 1993) 63 27291650
2012 The histone methyltransferase Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) is involved in human carcinogenesis. Genes, chromosomes & cancer 59 23011637
2012 The methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition. The Journal of biological chemistry 53 23269674
2017 The methyltransferase NSD3 promotes antiviral innate immunity via direct lysine methylation of IRF3. The Journal of experimental medicine 51 29101251
2012 No one can whistle a symphony alone - how different ubiquitin linkages cooperate to orchestrate NF-κB activity. Journal of cell science 51 22389394
2001 WHSC1L1, on human chromosome 8p11.2, closely resembles WHSC1 and maps to a duplicated region shared with 4p16.3. Genomics 50 11549311
2021 A NSD3-targeted PROTAC suppresses NSD3 and cMyc oncogenic nodes in cancer cells. Cell chemical biology 47 34469831
2009 NUP98-NSD3 fusion gene in radiation-associated myelodysplastic syndrome with t(8;11)(p11;p15) and expression pattern of NSD family genes. Cancer genetics and cytogenetics 45 19380029
2022 The role of NSD1, NSD2, and NSD3 histone methyltransferases in solid tumors. Cellular and molecular life sciences : CMLS 43 35532818
2017 WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer. Scientific reports 43 28102297
2014 NSD3-NUT-expressing midline carcinoma of the lung: first characterization of primary cancer tissue. Pathology, research and practice 39 25466466
2016 Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over-expression in breast cancer. Molecular oncology 38 27005559
2016 WHSC1L1 drives cell cycle progression through transcriptional regulation of CDC6 and CDK2 in squamous cell carcinoma of the head and neck. Oncotarget 38 27285764
2013 PPAPDC1B and WHSC1L1 are common drivers of the 8p11-12 amplicon, not only in breast tumors but also in pancreatic adenocarcinomas and lung tumors. The American journal of pathology 34 24051013
2005 Evaluation of NSD2 and NSD3 in overgrowth syndromes. European journal of human genetics : EJHG 33 15483650
2015 Cytological Features of a Variant NUT Midline Carcinoma of the Lung Harboring the NSD3-NUT Fusion Gene: A Case Report and Literature Review. Case reports in pathology 32 25685583
2022 Discovery of a potent and selective proteolysis targeting chimera (PROTAC) degrader of NSD3 histone methyltransferase. European journal of medicinal chemistry 31 35717870
2022 Thyroid Carcinoma with NSD3::NUTM1 Fusion: a Case with Thyrocyte Differentiation and Colloid Production. Endocrine pathology 27 34997561
2017 Amplification of the NSD3-BRD4-CHD8 pathway in pelvic high-grade serous carcinomas of tubo-ovarian and endometrial origin. Molecular and clinical oncology 25 28781807
2022 NUTM1 -rearranged Carcinoma of the Thyroid : A Distinct Subset of NUT Carcinoma Characterized by Frequent NSD3 - NUTM1 Fusions. The American journal of surgical pathology 24 36040068
2018 The role of histone lysine methyltransferase NSD3 in cancer. OncoTargets and therapy 24 30013365
2017 Silencing of histone methyltransferase NSD3 reduces cell viability in osteosarcoma with induction of apoptosis. Oncology reports 24 28901481
2014 Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity. Molecular biology of the cell 22 25318671
2019 Downregulation of NSD3 (WHSC1L1) inhibits cell proliferation and migration via ERK1/2 deactivation and decreasing CAPG expression in colorectal cancer cells. OncoTargets and therapy 19 31190890
2017 Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3. Breast cancer research and treatment 18 28484924
2018 Development of a Time-Resolved Fluorescence Resonance Energy Transfer Ultrahigh-Throughput Screening Assay for Targeting the NSD3 and MYC Interaction. Assay and drug development technologies 16 29634317
2024 Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation. Genome biology 14 39390582
2021 NSD3-NUTM1-rearranged carcinoma of the median neck/thyroid bed developing after recent thyroidectomy for sclerosing mucoepidermoid carcinoma with eosinophilia: report of an extraordinary case. Virchows Archiv : an international journal of pathology 14 33891143
2023 NSD3: Advances in cancer therapeutic potential and inhibitors research. European journal of medicinal chemistry 13 37182335
2021 Structure, Activity and Function of the NSD3 Protein Lysine Methyltransferase. Life (Basel, Switzerland) 13 34440470
2006 The histone methyltransferase activity of WHISTLE is important for the induction of apoptosis and HDAC1-mediated transcriptional repression. Experimental cell research 13 17239852
2024 Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 39119928
2022 Dissecting the Immunological Profiles in NSD3-Amplified LUSC through Integrative Multi-Scale Analyses. Cancers 11 36291782
2021 WHISTLE server: A high-accuracy genomic coordinate-based machine learning platform for RNA modification prediction. Methods (San Diego, Calif.) 11 34245870
2016 The PWWP domain of the human oncogene WHSC1L1/NSD3 induces a metabolic shift toward fermentation. Oncotarget 11 28903324
2021 WHISTLE: A Functionally Annotated High-Accuracy Map of Human m6A Epitranscriptome. Methods in molecular biology (Clifton, N.J.) 9 33835461
2023 Identification of novel class inhibitors of NSD3 methyltransferase showing a unique, bivalent binding mode in the SET domain. Chemical biology & drug design 8 37072259
2021 High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach. Journal of personalized medicine 8 34357103
2019 Protective effect of histone methyltransferase NSD3 on ISO-induced cardiac hypertrophy. FEBS letters 7 31254363
2024 NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions. International journal of molecular sciences 6 38256018
2010 A case of autologous microfat grafting in lip reconstruction of a whistle deformity following cancer treatment. The Canadian journal of plastic surgery = Journal canadien de chirurgie plastique 6 22131849
2023 Prospect of targeting lysine methyltransferase NSD3 for tumor therapy. Pharmacological research 5 37400043
2022 Rhabdomyosarcoma With Epithelioid Features And NSD3::FOXO1 Fusion: Evidence For Reconsideration Of Previously Reported FOXO1::FGFR1 Fusion. International journal of surgical pathology 5 35502835
2022 Possible Primary Thyroid Nuclear Protein in Testis Carcinomas with NSD3::NUTM1 Translocation Revealed by RNA Sequencing: A Report of Two Cases. Thyroid : official journal of the American Thyroid Association 5 35880417
2023 The histone methyltransferase NSD3 contributes to sister chromatid cohesion and to cohesin loading at mitotic exit. Journal of cell science 4 37288770
2023 WHSC1L1-mediated epigenetic downregulation of VMP1 participates in herpes simplex virus 1 infection-induced mitophagy impairment and neuroinflammation. Molecular immunology 4 37748280
2024 NSD3::NUTM1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Prolonged Survival. Biomedicines 3 39200173
2024 Targeted RNA sequencing in diagnostically challenging head and neck carcinomas identifies novel MON2::STAT6, NFATC2::NUTM2B, POC5::RAF1, and NSD3::NCOA2 gene fusions. Histopathology 3 39628352
2023 Systematic perturbations of SETD2, NSD1, NSD2, NSD3 and ASH1L reveals their distinct contributions to H3K36 methylation. bioRxiv : the preprint server for biology 3 37905045
2019 High yield recombinant expression and purification of oncogenic NSD1, NSD2, and NSD3 with human influenza hemagglutinin tag. Protein expression and purification 3 31563542
2025 NSD3::FGFR1 : A Novel Gene Fusion First to Be Described in Merkel Cell Carcinoma. The American Journal of dermatopathology 2 40036479
2025 Acquisition of FGFR1 and NSD3 Amplifications During the Transformation of EGFR-Mutated Lung Adenocarcinoma into Squamous Cell Carcinoma: A Case Report. JTO clinical and research reports 2 40792216
2021 Histone Methyltransferase NSD3 Is a Lung Squamous Cell Carcinoma Driver. Cancer discovery 2 33579784
2014 Wetting the whistle: neurotropic factor improves salivary function. The Journal of clinical investigation 2 25036702
2025 NSD3: A Promising Target for Cancer Therapy. Cell biochemistry and function 1 40143436
2025 H3K36 histone methyltransferase NSD3 functions as a multifaceted regulator of late erythropoiesis. Biochemical and biophysical research communications 1 40532307
2025 Isoform-specific function of NSD3 in DNA replication stress confers resistance to PARP inhibitors in prostate cancer. Molecular cell 1 40578344
2025 The histone lysine methyltransferase NSD3 drives osteosarcomagenesis by inactivating ARID3A. Cancer letters 1 40967468
2024 Structural insights into the C-terminus of the histone-lysine N-methyltransferase NSD3 by small-angle X-ray scattering. Frontiers in molecular biosciences 1 38516186
2022 Degradation of NSD3: What to Myc of it all? Cell chemical biology 1 35303440
2026 NSD3 stabilizes nuclear compartmentalization and promotes megabase-scale chromatin interactions. bioRxiv : the preprint server for biology 0 41727024
2026 Fluorogenic Ligand Enables Identification of NSD3-Overexpressed Tumors by Targeting the PWWP1 Domain of NSD3. Analytical chemistry 0 41820229
2026 Histone methyltransferase G9a crosstalks with H3K36 histone methyltransferases NSD3 and SETD2 to mediate gene activation. Frontiers in cell and developmental biology 0 41970952
2025 NSD3::NUTM1 fusion evidenced on RNA sequencing in poorly differentiated thyroid cancer: a report of two cases. European thyroid journal 0 40990092
2025 Histone methyltransferase NSD3 orchestrates early erythropoiesis by regulating erythroid progenitor cell differentiation and survival. Biochimica et biophysica acta. Molecular cell research 0 41360235
2024 Thyroid Carcinoma With NSD3::NUTM1 Fusion and Secondary TERT Promoter Mutation: A Case Report and Literature Review. International journal of surgical pathology 0 39285723
2024 NSD3 protein methylation and stabilization transforms human ES cells into variant state. Life science alliance 0 39741006
2018 [NSD3 suppresses LPS-triggered TNF-α production via promoting the dimethylation of histone H3K36 in macrophages]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 30236198