Affinage

NSD2

Histone-lysine N-methyltransferase NSD2 · UniProt O96028

Length
1365 aa
Mass
152.3 kDa
Annotated
2026-04-29
100 papers in source corpus 46 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NSD2 (MMSET/WHSC1) is a histone H3K36 dimethyltransferase that catalyzes broad intergenic H3K36me2 deposition on nucleosomal substrates via an SN2 methyl-transfer mechanism, with an autoinhibitory loop that opens upon nucleosome engagement to grant access to H3K36; its overexpression or activating mutations (E1099K, T1150A) drive global H3K36me2 expansion with reciprocal H3K27me3 reduction, reprogramming enhancer landscapes, CTCF binding, and gene expression to promote oncogenesis in multiple myeloma, ALL, prostate cancer, and lung adenocarcinoma (PMID:34782608, PMID:24076604, PMID:25188243, PMID:31649247, PMID:34555356). Beyond histone methylation, NSD2 methylates non-histone substrates including PTEN-K349 (facilitating 53BP1-mediated DSB repair) and STAT3-K163 (promoting angiogenesis), and is recruited to DNA damage sites via γH2AX–MDC1 interaction to deposit H4K20me2 and H3K36me2 that promote NHEJ, HR, and nucleotide excision repair (PMID:21293379, PMID:31217297, PMID:33742125, PMID:27109101, PMID:29233865). NSD2 also functions in a catalytic-activity-independent manner as a scaffold at enhancers with BRD4 during germ-layer specification, interacts with NLRC5 to drive MHC-I antigen presentation, and serves as a requisite subunit of the AR/FOXA1 neo-enhanceosome at tumor-specific prostate cancer enhancers (PMID:31235934, PMID:35230972, PMID:39251788). NSD2 protein stability is regulated by CRL4Cdt2-dependent S-phase degradation counteracted by AKT-mediated phosphorylation at S172, and its enzymatic activity is inhibited by PARP1-mediated PARylation (PMID:26771714, PMID:28319045, PMID:31248990).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Identification of NSD2 as the gene disrupted by the t(4;14) translocation in multiple myeloma established it as a candidate oncogene and revealed its multi-domain architecture (HMG, PHD fingers, SET domain).

    Evidence Molecular cloning and translocation breakpoint mapping in MM patient samples

    PMID:9787135

    Open questions at the time
    • Enzymatic activity of the SET domain was unknown
    • Oncogenic mechanism was not established
  2. 2005 High

    Functional loss-of-function studies and localization experiments demonstrated that NSD2 overexpression is required for myeloma cell proliferation and colony formation, and that it acts as a transcriptional repressor recruiting HDAC1/mSin3b, while breakpoint-variant isoforms show aberrant nucleolar localization.

    Evidence RNAi knockdown, gene targeting of translocated allele, co-immunoprecipitation, reporter assays, GFP-tagging and FRAP in MM cells

    PMID:15677557 PMID:16197452 PMID:17942756

    Open questions at the time
    • Histone substrate specificity was unresolved
    • Whether repression required catalytic activity was unclear
  3. 2007 High

    Biochemical characterization revealed NSD2 possesses histone methyltransferase activity (H4K20 in cells, H3K4/H4K20 in vitro) and forms a repressive complex with HDAC1, HDAC2, mSin3a, and LSD1, while an alternatively transcribed isoform (RE-IIBP) showed H3K27 methyltransferase activity.

    Evidence In vitro methyltransferase assays, co-immunoprecipitation, Gal4-reporter assays, active-site mutagenesis

    PMID:18156491 PMID:18172012

    Open questions at the time
    • The primary physiological histone substrate (H3K36me2) had not yet been identified
    • Specificity for H3K27 was later disputed
  4. 2011 High

    Discovery of NSD2 recruitment to DNA double-strand breaks via the γH2AX–MDC1 pathway, where it deposits H4K20me2 to facilitate 53BP1 accumulation, established a direct role in the DNA damage response.

    Evidence Co-immunoprecipitation of phospho-S102 NSD2 with MDC1 BRCT domain, laser-induced DSB recruitment, ChIP

    PMID:21293379

    Open questions at the time
    • Whether NSD2 also deposited H3K36me2 at DSBs was not shown
    • Relative contributions to NHEJ vs HR were unclear
  5. 2012 High

    Multiple studies converged on H3K36me2 as NSD2's principal mark in cancer, showing that NSD2 overexpression causes global H3K36me2 gain with reciprocal H3K27me3 loss, directly activates TWIST1 to drive EMT, represses miR-126* to upregulate c-MYC, and is required for class switch recombination via 53BP1 recruitment to Igh switch regions.

    Evidence ChIP at target loci (TWIST1, miR-126*), isogenic gain/loss-of-function in prostate and MM cells, CSR assays, epistasis with EZH2

    PMID:22797064 PMID:22972034 PMID:23159737 PMID:23241889

    Open questions at the time
    • Genome-wide distribution of H3K36me2 changes was not yet mapped
    • Whether H3K36me2 was primary or secondary to other marks was debated
  6. 2013 High

    Discovery of the E1099K activating mutation in pediatric ALL, confirmed by mass spectrometry histone profiling, established that NSD2 gain-of-function through point mutations (not just translocation/overexpression) drives oncogenesis via H3K36me2 expansion.

    Evidence Mass spectrometry histone profiling across >1000 cancer genomes, shRNA knockdown, xenograft

    PMID:24076604

    Open questions at the time
    • Structural basis for E1099K hyperactivation was unknown
    • Therapeutic vulnerabilities of NSD2-mutant cancers were unexplored
  7. 2014 High

    Genome-wide ChIP-seq revealed that NSD2 overexpression redistributes H3K36me2 globally while paradoxically enhancing EZH2 recruitment at specific loci, and that PHD domains mediate NSD2 chromatin recruitment and are required for these epigenetic changes and in vivo tumorigenesis.

    Evidence ChIP-seq in isogenic MM cell lines, PHD domain mutants, xenograft tumor regression

    PMID:25188243

    Open questions at the time
    • How PHD domains select target loci was unresolved
    • 3D genome consequences were not examined
  8. 2016 High

    Kinetic isotope effect measurements established that NSD2 catalyzes H3K36 dimethylation via an SN2 mechanism with a late asymmetric transition state, preferring dimethylation over monomethylation, while functional studies showed NSD2 is required for both NHEJ and HR and is regulated by CRL4Cdt2-dependent S-phase degradation.

    Evidence KIE measurements, quantum chemical modeling, NHEJ/HR reporter assays in isogenic MM lines, cell synchronization and degradation assays

    PMID:26771714 PMID:26787850 PMID:27109101

    Open questions at the time
    • Structural basis for nucleosome recognition was unknown
    • How degradation is counteracted in cancer was unclear
  9. 2017 High

    AKT-mediated phosphorylation at S172 was shown to stabilize NSD2 by blocking CRL4Cdt2-dependent degradation, creating a positive feedback loop through NSD2-driven RICTOR transcription that amplifies AKT/mTORC2 signaling in PTEN-null prostate cancer.

    Evidence In vivo PTEN-null mouse prostate cancer model, phosphorylation mapping, co-immunoprecipitation, ChIP

    PMID:28319045

    Open questions at the time
    • Whether other kinases phosphorylate NSD2 at additional sites was unknown
    • Therapeutic targeting of this feedback loop was not tested
  10. 2019 High

    NSD2 was found to methylate non-histone substrates—PTEN at K349 (read by 53BP1 tudor domain for DSB repair) and STAT3 at K163 (activating angiogenic signaling)—while PARP1-mediated PARylation was discovered to inhibit NSD2 catalytic activity and chromatin binding, and NSD2 was shown to have catalytic-activity-independent scaffolding roles (with BRD4 at mesendodermal enhancers) and immune functions (Tfh cell differentiation via Bcl6).

    Evidence MS-based methylation mapping, site-directed mutagenesis, in vitro methylation assays, BioID proximity labeling, conditional knockout with genetic rescue, ChIP

    PMID:31217297 PMID:31235934 PMID:31248990 PMID:31636135 PMID:31649247 PMID:33742125

    Open questions at the time
    • Full non-histone substrate repertoire was unknown
    • Whether scaffolding and enzymatic functions are separable in vivo was untested
  11. 2021 High

    Cryo-EM structure of NSD2 bound to the nucleosome revealed the autoinhibitory loop mechanism and how E1099K/T1150A mutations destabilize it, while a chemical probe (UNC6934) targeting the PWWP1 domain confirmed its role in reading H3K36me2 for chromatin retention and showed that PWWP1 antagonism redirects NSD2 to the nucleolus.

    Evidence Cryo-EM at near-atomic resolution, kinetic analysis, MD simulation, co-crystal structure of PWWP1/UNC6934, cellular imaging

    PMID:34782608 PMID:34782742

    Open questions at the time
    • Full-length NSD2 structure including all reader domains was not resolved
    • Whether PWWP1 antagonism is sufficient for therapeutic benefit was untested
  12. 2021 High

    NSD2 E1099K was shown to drive glucocorticoid resistance in pediatric ALL through H3K27me3 accumulation at the NR3C1 promoter (reversible by PRC2 inhibitors), while NSD2 cooperates with oncogenic KRAS to amplify transcriptional output in lung adenocarcinoma and functions as a requisite subunit of the AR/FOXA1 neo-enhanceosome at tumor-specific prostate cancer enhancers.

    Evidence CRISPR correction of E1099K, ChIP-seq, PRC2 inhibitor in PDX models, KRAS-driven LUAD mouse model, AR cistrome analysis with PROTAC degrader

    PMID:34417224 PMID:34555356 PMID:39251788

    Open questions at the time
    • Whether NSD2 inhibition synergizes with immunotherapy across cancers is unknown
    • How NSD2 is recruited to AR/FOXA1 sites mechanistically is incompletely defined
  13. 2022 Medium

    NSD2 was established as required for adipogenesis (preventing H3K27me3-mediated silencing of C/EBPα/PPARγ targets), for spermatogenesis (maintaining H3K36me2 and regulating histone eviction via PSMA8 interaction), and for regulatory T cell homing to the maternal-fetal interface via CXCR4 upregulation.

    Evidence Conditional knockouts in preadipocytes, spermatogenic cells, and Tregs; ChIP-seq; co-immunoprecipitation; fertility/pregnancy phenotyping

    PMID:29728617 PMID:35322173 PMID:35736136

    Open questions at the time
    • Whether NSD2's roles in these lineages are catalytic or scaffolding is incompletely resolved
    • Tissue-specific NSD2 target gene programs are not fully defined
  14. 2023 Medium

    Development of PROTAC degraders (UNC8153, UNC8732) demonstrated that targeted NSD2 degradation reduces H3K36me2, suppresses MM cell adhesion/proliferation, and reverses drug resistance in NSD2-mutant ALL, validating NSD2 as a druggable target.

    Evidence PROTAC degradation assays, FBXO22/cereblon dependency mapping, anti-proliferative assays in MM and ALL cells

    PMID:36976643 PMID:38965384

    Open questions at the time
    • In vivo pharmacokinetics and toxicity profiles are unreported
    • Selectivity over NSD1/NSD3 in therapeutic settings is uncharacterized
  15. 2024 High

    Systematic CRISPR knockout of all H3K36 methyltransferases established a functional hierarchy (NSD1 > NSD2 > NSD3 > ASH1L) for intergenic H3K36me2 deposition, with NSD2 being the second-most important enzyme for broad intergenic domains.

    Evidence Individual and combinatorial CRISPR KO of K36MTs, ChIP-seq for H3K36me1/2/3, RNA-seq in mouse mesenchymal stem cells

    PMID:39390582

    Open questions at the time
    • Whether this hierarchy is conserved across all human cell types is untested
    • Compensation mechanisms among NSD family members are incompletely understood

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full non-histone substrate repertoire, the structural basis for how reader domains (PHD, PWWP) coordinate locus-specific targeting genome-wide, whether catalytic and scaffolding functions can be therapeutically separated, and the in vivo efficacy and selectivity of NSD2-targeted degraders.
  • No full-length NSD2 structure with all reader domains
  • Comprehensive non-histone substrate profiling has not been performed
  • In vivo therapeutic index of NSD2-selective degraders or inhibitors is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-4839726 Chromatin organization 6 R-HSA-73894 DNA Repair 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2
Partners
ARBRD4HDAC1MDC1NLRC5PARP1PTENSMARCA2
Complex memberships
AR/FOXA1 neo-enhanceosomeHDAC1/HDAC2/LSD1/mSin3a repressor complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MMSET (NSD2) was identified as a novel gene disrupted by the t(4;14)(p16.3;q32.3) translocation in multiple myeloma. The long form (1365 aa) contains HMG box, hath region, 4 PHD fingers, and a SET domain, while a short form (647 aa) contains the HMG box and hath region. The translocation results in IgH/MMSET hybrid transcripts and overexpression from endogenous promoters. Molecular cloning, RT-PCR, domain analysis, translocation breakpoint mapping Blood High 9787135
2001 A mRNA initiated within the middle intron of WHSC1/MMSET encodes RE-IIBP, a protein containing a SET domain and two PHD-type zinc fingers that specifically binds the IL-5 response element RE-II and represses IL-5 transcription when expressed in activated T cells. Expression cloning, EMSA, 5'-RACE, transfection reporter assays, luciferase reporter American journal of respiratory cell and molecular biology Medium 11152655
2005 MMSET I isoform represses transcription of a chromatin-embedded reporter gene in a dose-dependent manner and specifically recruits HDAC1 and mSin3b (but not HDAC2 or HDAC4) as shown by co-immunoprecipitation; HDAC inhibitor trichostatin A reduces repression activity. Co-immunoprecipitation, transcriptional reporter assays, HDAC inhibitor treatment British journal of haematology Medium 16197452
2005 All transcripts from the WHSC1/MMSET/NSD2 locus are uniformly overexpressed in t(4;14)+ myeloma patients. GFP-tagged MMSET I and II localize to the nucleus (not nucleoli), while MB4-2 and MB4-3 breakpoint variant proteins concentrate in nucleoli. FRAP kinetic studies show breakpoint variants are functionally distinct from wild-type proteins. Exon 4a/MMSET III contains a domain that prevents nucleolar localization. Quantitative RT-PCR, GFP-tagging, fluorescence live-cell imaging, FRAP Blood Medium 15677557
2007 MMSET possesses histone methyltransferase activity for H3K4 and H4K20 in vitro; in cells, MMSET modifies only H4K20. MMSET fused to Gal4 DNA-binding domain represses transcription of a chromatin-embedded reporter, associated with increased H4K20 methylation and loss of histone acetylation. MMSET forms a complex with HDAC1, HDAC2, mSin3a, and the histone demethylase LSD1. In vitro methyltransferase assay, Gal4-reporter transcription assay, co-immunoprecipitation Blood High 18156491
2007 MMSET knockdown by RNAi and selective disruption of the translocated MMSET allele by gene targeting dramatically reduced colony formation in methylcellulose, caused cell-cycle arrest of adherent MM cells, reduced adhesion to extracellular matrix, and reduced tumor formation in xenografts. RNAi knockdown, gene targeting/knockout, colony formation assay, xenograft mouse model Blood High 17942756
2008 RE-IIBP (an MMSET isoform) has histone H3K27 methyltransferase activity; SET domain residues C483 and R477 are critical for this activity. RE-IIBP represses transcription via HDAC recruitment mediated by H3K27 methylation, demonstrated at the IL-5 promoter by ChIP showing increased H3K27me, HDAC recruitment, and H3 hypoacetylation. In vitro HMTase assay, point mutant analysis, ChIP, luciferase reporter Molecular and cellular biology High 18172012
2009 NSD2 specifically interacts with the DNA-binding domain of androgen receptor (AR) via its HMG domain. Nuclear translocation of both NSD2 and AR is enhanced in the presence of ligand. NSD2 overexpression, but not the SET-domain mutant (ΔSET, HMT-defective), enhances PSA mRNA levels. ChIP showed NSD2 is recruited to the PSA gene enhancer by AR in an agonist-dependent manner. Co-immunoprecipitation, ChIP, qRT-PCR, domain deletion mutant FEBS letters Medium 19481544
2011 MMSET (NSD2) is recruited to DNA double-strand breaks (DSBs) via interaction between the MDC1 BRCT domain and phosphorylated Ser102 of MMSET, dependent on the γH2AX-MDC1 pathway. Once recruited, MMSET mediates local H4K20 dimethylation at DSBs, which facilitates 53BP1 accumulation at damage sites. Co-immunoprecipitation, ChIP, shRNA knockdown, laser-induced DSBs, immunofluorescence Nature High 21293379
2012 MMSET knockdown in prostate cancer cells decreased H3K36me2 and H3K27me3, reduced cell migration and invasion, and blocked EMT. MMSET overexpression in non-transformed RWPE-1 cells promoted invasion and EMT. ChIP showed MMSET binds the TWIST1 locus and increases H3K36me2, directly activating TWIST1 expression, which is the critical mediator of MMSET-driven invasion. ChIP, shRNA knockdown, overexpression, invasion/migration assays, EMT marker analysis Oncogene High 22797064
2012 EZH2 functions upstream of MMSET in a coordinated HMTase axis regulated by a microRNA network. EZH2-mediated H3K27me3 and MMSET-mediated H3K36me2 are coordinately regulated, and the oncogenic functions of EZH2 require MMSET activity. Genetic knockdown epistasis, microRNA overexpression/inhibition, ChIP Molecular cell Medium 23159737
2012 MMSET promotes proliferation of multiple myeloma cells by stimulating c-MYC expression at the post-transcriptional level. MMSET represses miR-126* by binding to its promoter along with the KAP1 corepressor and HDACs, leading to heterochromatic modifications (increased H3K9me3, decreased H3 acetylation). miR-126* targets the 3'-UTR of c-MYC mRNA to inhibit its translation. miRNA profiling, ChIP, luciferase 3'-UTR reporter assay, miRNA overexpression Leukemia Medium 22972034
2012 MMSET plays an important role in class switch recombination (CSR) through its histone methyltransferase activity. MMSET knockdown impaired 53BP1 recruitment to Igh switch regions and decreased germline transcription of switch regions, resulting in defective CSR without affecting cell growth or viability. shRNA knockdown, CSR assay, 53BP1 recruitment immunofluorescence, germline transcription RT-PCR Journal of immunology Medium 23241889
2013 NSD2 methyltransferase activity is crucial for clonogenicity, adherence, and proliferation of multiple myeloma cells on bone marrow stroma. The PHD domains of NSD2 are required for its cellular activity and recruit NSD2 to oncogenic target gene loci to drive their transcriptional activation. PHD domain mutants, ChIP, colony formation, proliferation assays, xenograft Cancer research Medium 23980095
2013 NSD2 p.E1099K is an activating mutation that increases H3K36 dimethylation and promotes transformation; NSD2 knockdown selectively inhibits proliferation of NSD2-mutant ALL cell lines and impairs in vivo growth of NSD2-mutant ALL xenografts. Global histone profiling by mass spectrometry identified the distinct H3K36me2 signature of NSD2 hyperactivation. High-information-content mass spectrometry histone profiling, ectopic expression, shRNA knockdown, xenograft Nature genetics High 24076604
2014 MMSET overexpression causes a global increase in H3K36me2 and a global reduction of H3K27me3. Despite net decrease in H3K27me3, specific loci show enhanced EZH2 recruitment and become hypermethylated on H3K27. PHD domains of MMSET mediate its chromatin recruitment and are required for these epigenetic changes. ChIP-seq, shRNA inducible knockdown, PHD domain mutants, xenograft tumor regression PLoS genetics High 25188243
2014 Whsc1 promotes the association of Runx2 and p300 to activate bone-related genes (Osteopontin, Col1a1). Whsc1 suppresses overactivation of these genes via H3K36 trimethylation. Whsc1-/- embryos exhibit defects in ossification, and Whsc1 knockdown in pre-osteoblasts perturbs histone modification patterns at bone-related gene loci. Co-immunoprecipitation (Runx2/p300 association), ChIP, Whsc1 knockout mouse, siRNA knockdown, bone differentiation assays PloS one Medium 25188294
2016 NSD2 catalyzes H3K36 dimethylation via an SN2 mechanism where methyl transfer is the first irreversible chemical step. The transition state is a late, asymmetric nucleophilic displacement with bond separation from the leaving group at 2.53 Å and bond making to the attacking nucleophile at 2.10 Å. NSD2 preferentially catalyzes H3K36 dimethylation over monomethylation. Kinetic isotope effect measurements, quantum chemical/computational modeling, in vitro enzymatic assay with nucleosome substrate Proceedings of the National Academy of Sciences of the United States of America High 26787850
2016 MMSET is required for efficient non-homologous end joining (NHEJ) and homologous recombination (HR). Loss of MMSET leads to loss of expression of several DNA repair proteins and decreased recruitment of DNA repair proteins to DSB sites. MMSET-high cells repair DNA damage at enhanced rate compared to MMSET-low isogenic cells. NHEJ/HR reporter assays, immunofluorescence of DNA repair factor recruitment, isogenic MM cell line pairs, xenograft Oncogene High 27109101
2016 MMSET is degraded during S phase in a CRL4(Cdt2)- and proteasome-dependent manner. MMSET depletion causes defects in DNA replication and decreased association of pre-replication complex (pre-RC) factors with chromatin, indicating a role for MMSET in normal DNA replication. Cell synchronization, co-immunoprecipitation, chromatin fractionation, DNA fiber assay Cell cycle Medium 26771714
2016 NSD2 (methyltransferase-active) is recruited to promoters of glucose metabolic enzyme genes (HK2, G6PD, TIGAR) and methylates H3K36me2 at these loci, coordinately upregulating their expression to drive pentose phosphate pathway activity and endocrine resistance in breast cancer. Methylase-defective NSD2 mutant cannot drive resistance. ChIP, gene expression profiling, methylase-dead mutant, xenograft, PPP activity assay Cancer letters Medium 27164560
2017 AKT phosphorylates WHSC1 at S172 upon PTEN loss, preventing its degradation by CRL4Cdt2 E3 ligase. Increased WHSC1 transcriptionally upregulates RICTOR (mTORC2 component) to further enhance AKT activity, forming a feedback loop. WHSC1 also positively regulates Rac1 transcription to increase tumor cell motility. In vivo mouse PCa model (PTEN-null + WHSC1 overexpression), genetic ablation, phosphorylation mapping, co-immunoprecipitation, ChIP The Journal of clinical investigation High 28319045
2017 DICER mediates the recruitment of MMSET to UV-induced DNA damage sites. MMSET is required for efficient nucleotide excision repair (NER) by catalyzing H4K20me2 at DNA damage sites, which facilitates recruitment of the NER factor XPA. Immunofluorescence at UV damage sites, MMSET knockdown, ChIP, XPA recruitment assay The Journal of cell biology Medium 29233865
2018 The NSD2 E1099K mutation alters enzyme/substrate binding and enhances the rate of H3K36 methylation in vitro. E1099K cells exhibit increased H3K36me2, reduced H3K27me3 (particularly on H3.1-containing nucleosomes), reduced apoptosis, and enhanced proliferation, clonogenicity, adhesion, migration, and brain invasion in xenografts. Gene-edited isogenic cell lines, in vitro enzymatic assay, transcriptional profiling, xenograft Oncogene High 30171259
2019 DNA DSBs promote NSD2-mediated dimethylation of PTEN at K349; this methylation is recognized by the tudor domain of 53BP1 to recruit PTEN to DNA-damage sites, governing efficient DSB repair partly through dephosphorylation of γH2AX. ATM-dependent phosphorylation of T/S398-PTEN promotes PTEN interaction with MDC1 upstream of NSD2 activity. Co-immunoprecipitation, mass spectrometry methylation mapping, site-directed mutagenesis, in vitro methylation assay, xenograft Cancer discovery High 31217297
2019 NSD2 promotes tumor angiogenesis by methylating STAT3 at K163; mass spectrometry and site-directed mutagenesis confirmed this methylation site. K163R STAT3 mutant shows attenuated activation and angiogenic function. NSD2 promotes STAT3 activation through a methylation-phosphorylation regulation pattern, driving VEGFA expression. Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis (K163R), in vitro methylation assay, angiogenesis assays Oncogene Medium 33742125
2019 NSD2 overexpression drives chromatin and transcriptional changes linked to oncogene activation within insulated topological domains. NSD2-driven expansion of H3K36me2 leads to alterations in H3K27ac and CTCF binding within H3K36me2-enriched chromatin, and differentially expressed genes are significantly enriched within the same insulated domain as altered H3K27ac and CTCF peaks. ChIP-seq, Hi-C/3D genome organization, isogenic cell lines (high vs. low NSD2), logistic regression modeling Nature communications Medium 31649247
2019 PARP1 directly interacts with NSD2 (identified by BioID proximity labeling and MS). Upon oxidative stress, PARP1 PARylates NSD2, which significantly reduces NSD2 histone methyltransferase activity in vitro and inhibits NSD2 binding to nucleosomes and its recruitment to NSD2-regulated gene loci. BioID proximity labeling, mass spectrometry, in vitro methyltransferase assay, nucleosome binding assay, ChIP The Journal of biological chemistry High 31248990
2019 Whsc1 (NSD2) is required for follicular helper T (Tfh) cell differentiation. CD28 signaling induces Nsd2 expression, which is required for Bcl6 expression as early as the first cell division after T cell activation. Nsd2 deficiency impairs Tfh generation, germinal center response, and virus clearance. Ectopic Bcl6 expression rescues the Tfh defect of Nsd2 KO cells. Conditional knockout, Bcl6 rescue experiment, germinal center assays, flow cytometry The Journal of experimental medicine Medium 31636135
2019 Whsc1 has a dual role in pluripotency exit and germ layer specification in mouse embryonic stem cells. Whsc1 binds to enhancers of mesendodermal regulators (Gata4, Brachyury, Gata6, Foxa2) together with Brd4 to activate their expression. Notably, these functions are independent of Whsc1 methyltransferase activity. Conditional depletion, ChIP, co-immunoprecipitation with Brd4, directed differentiation assays, methyltransferase-dead mutant Nature cell biology Medium 31235934
2020 NSD2 knockdown in primary human fibroblasts induces cellular senescence via RB-mediated downregulation of cell cycle-related genes. NSD2 is enriched at gene bodies of actively transcribed genes including cell cycle-related genes, and NSD2 loss decreases H3K36me3 at these loci. Serum stimulation upregulates NSD2 and induces cell cycle gene expression. RNAi screen, ChIP, transcriptome analysis, senescence assays (SA-β-gal, mitochondrial mass) Aging cell Medium 32573059
2020 MMSET promotes H3K36me2 at deprotected telomeres through its SET-domain catalytic activity, and this promotes classical (Ligase4-dependent) NHEJ at deprotected telomeres. MMSET-dependent H3K36me2 levels directly correlate with NHEJ efficiency; MMSET depletion does not affect upstream DDR recognition but acts downstream at the repair step. Methyltransferase screen, MMSET knockdown, telomere dysfunction assay, ChIP, Ligase4-dependent NHEJ assay Oncogene Medium 32472076
2021 Cryo-EM structure of NSD2 bound to the nucleosome reveals that nucleosomal DNA is partially unwrapped to facilitate NSD2 access to H3K36. NSD2 interacts with DNA, H2A, and H3. The autoinhibitory loop changes conformation upon nucleosome binding to accommodate H3 in the substrate-binding cleft. E1099K and T1150A oncogenic mutations increase catalytic turnover by destabilizing interactions that keep the autoinhibitory loop closed. Cryo-electron microscopy structure determination, kinetic analysis, molecular dynamics simulation Nature communications High 34782608
2021 NSD2 PWWP1 domain occupies a canonical H3K36me2-binding pocket. A chemical probe (UNC6934) targeting PWWP1 antagonizes its interaction with nucleosomal H3K36me2 and induces accumulation of endogenous NSD2 in the nucleolus, phenocopying localization defects of NSD2 isoforms lacking PWWP1 (as occur in t(4;14) MM). Mutations in other NSD2 chromatin reader domains also increase NSD2 nucleolar localization. Chemical probe (UNC6934), co-crystal structure of PWWP1/probe, cellular NSD2 localization by imaging, nucleosome-binding assays Nature chemical biology High 34782742
2021 NSD2 E1099K mutation drives glucocorticoid resistance in pediatric ALL by causing H3K27me3 accumulation at the NR3C1 (glucocorticoid receptor) promoter, repressing GR expression and blocking GR autoactivation. PRC2 inhibitors remove this H3K27me3, restore NR3C1 expression, and reverse glucocorticoid resistance in vitro and in vivo. High-throughput drug screening, CRISPR correction of E1099K, ChIP-seq, PRC2 inhibitor treatment, PDX model Cancer discovery High 34417224
2021 NSD2 interacts with SMARCA2 (SWI/SNF ATPase subunit) in a non-canonical, SWI/SNF complex-independent manner. The NSD2-SMARCA2 complex is mapped to the PTP4A3 promoter by ChIP, leading to focal H3K36me2 increase and transcriptional activation of PTP4A3, which maintains MYC expression. BET inhibitor PFI-3 displaces NSD2 from the PTP4A3 promoter. SILAC-based mass spectrometry interactome, co-immunoprecipitation, ChIP, RNA-seq Cancer research Medium 33602783
2021 NSD2 via H3K36me2 catalysis cooperates with oncogenic KRAS signaling to drive lung adenocarcinoma (LUAD) pathogenesis in vivo. NSD2E1099K expression accelerates malignant tumor progression in KRAS-driven LUAD mouse models. Pathologic H3K36me2 generation amplifies transcriptional output of KRAS and complementary oncogenic gene expression programs. In vivo LUAD mouse model, CRISPRi-based knockdown, PDX model, MEK inhibitor combination, ChIP-seq Molecular cell High 34555356
2021 WHSC1 loss impairs IFN-γ-stimulated antitumor immunity by transcriptionally downregulating MHC-I machinery without affecting PD-L1. WHSC1 directly interacts with NLRC5 to promote MHC-I gene expression. IFN-γ/STAT1 signaling stimulates WHSC1 expression, which in turn promotes NLRC5-dependent antigen presentation. Co-immunoprecipitation (WHSC1-NLRC5), shRNA knockdown, CRC organoids, xenografts, Apcmin/+ mouse model The Journal of clinical investigation High 35230972
2021 Loss-of-function and missense NSD2 variants cause reduced H3K36 methyltransferase activity in vitro; missense variants fail to reconstitute H3K36me2 in NSD2 knockout cells. Structural modeling indicates interference with NSD2 folding and function for missense variants in known structural domains. In vitro methylation assay, NSD2 KO cell complementation, in silico structural modeling Genetics in medicine Medium 33941880
2022 Nsd2 (but not Nsd1 or Setd2) is required for adipogenesis; depletion of Nsd2 in preadipocytes phenocopies H3.3K36M effects by increasing H3K27me3 to prevent induction of C/EBPα and PPARγ target genes. In differentiated adipocytes, Nsd2 loss does not affect tissue weight but leads to BAT whitening and insulin resistance in WAT. shRNA knockdown of Nsd2/Nsd1/Setd2 (selective comparison), H3.3K36M expression, adipogenesis assays, in vivo mouse models, ChIP Nature communications High 29728617
2022 Nsd2 deficiency in mouse spermatogenic cells reduces H3K36me2 and H3K36me3 genome-wide, with H3K36me2 occupancy positively correlating with germline gene expression. Nsd2 loss leads to H4K16ac elevation through interaction with PSMA8 (which regulates acetylated histone degradation), impairs EP300-induced H4K5/8ac and BRDT-mediated histone eviction, causing histone retention in spermatozoa. Conditional knockout, ChIP-seq, co-immunoprecipitation (NSD2-PSMA8), spermatogenesis assays, fertility phenotype Nucleic acids research Medium 35736136
2022 Nsd2 upregulates CXCR4 expression via H3K36me2 modification to promote regulatory T cell recruitment to the maternal-fetal interface. Nsd2 conditional KO in Tregs specifically reduces Treg levels at the decidua and causes fetal loss without affecting systemic Treg development or function. Conditional knockout, ChIP (H3K36me2 at CXCR4 locus), Treg recruitment assay, pregnancy model Cellular & molecular immunology Medium 35322173
2023 NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in prostate cancer. Tumor-specific AR enhancers critically rely on NSD2's H3K36 dimethyltransferase activity. NSD2 inactivation disrupts over 65% of AR cistrome; NSD2-dependent AR sites harbor a chimeric FOXA1:AR half-motif exclusive to tumor-specific enhancers. ChIP-seq (AR, NSD2, H3K36me2), NSD2 inactivation, AR cistrome analysis, PROTAC degrader, patient specimens Nature genetics High 39251788
2023 NSD2 is selectively degraded by a PROTAC (UNC8153) through a novel mechanism via a simple warhead, and separately by UNC8732 through FBXO22 recruitment (FBXO22's C326 is engaged by an aldehyde metabolite). Both degraders reduce H3K36me2, suppress MM cell adhesion and proliferation, and cause apoptosis and drug resistance reversal in NSD2-mutant ALL cells. PROTAC degradation assay, proteasome/cereblon/FBXO22 dependence assays, H3K36me2 western blot, anti-proliferative assays Journal of the American Chemical Society / Nature chemical biology Medium 36976643 38965384
2024 Systematic perturbation of H3K36 methyltransferases established that NSD2 (along with NSD1) is responsible for deposition of broad intergenic H3K36me2 domains, while NSD3 deposits H3K36me2 peaks on active promoters and enhancers. A hierarchy of K36MT activities was determined: NSD1 > NSD2 > NSD3 > ASH1L for intergenic H3K36me1/2 deposition. CRISPR knockout of individual K36MTs, ChIP-seq (H3K36me1/2/3), RNA-seq, mouse mesenchymal stem cells Genome biology High 39390582

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood 442 9787135
2011 MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. Nature 334 21293379
2013 Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nature genetics 228 24076604
2014 Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation. PLoS genetics 198 25188243
2007 The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor. Blood 160 18156491
2005 Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients. Blood 146 15677557
2002 A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood 141 12433679
2012 The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial-mesenchymal transition and invasive properties of prostate cancer. Oncogene 138 22797064
2007 The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity. Blood 133 17942756
2012 Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer. Molecular cell 124 23159737
2011 The histone methyltransferase and putative oncoprotein MMSET is overexpressed in a large variety of human tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 120 21385930
2017 AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis. The Journal of clinical investigation 108 28319045
2008 MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells. Haematologica 100 19059936
2019 NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling. The Journal of pathology 82 30666650
2008 Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity. Molecular and cellular biology 82 18172012
2020 CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer. Journal of cellular and molecular medicine 79 32378344
2016 MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents. Oncogene 76 27109101
2021 NSD2 dimethylation at H3K36 promotes lung adenocarcinoma pathogenesis. Molecular cell 74 34555356
2012 MMSET stimulates myeloma cell growth through microRNA-mediated modulation of c-MYC. Leukemia 74 22972034
2018 Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function. Nature communications 73 29728617
2019 PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage. Cancer discovery 72 31217297
2016 Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes. Cancer letters 72 27164560
2021 A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization. Nature chemical biology 71 34782742
2019 NSD2 overexpression drives clustered chromatin and transcriptional changes in a subset of insulated domains. Nature communications 68 31649247
2022 Histone methyltransferase WHSC1 loss dampens MHC-I antigen presentation pathway to impair IFN-γ-stimulated antitumor immunity. The Journal of clinical investigation 67 35230972
2015 Unabridged Analysis of Human Histone H3 by Differential Top-Down Mass Spectrometry Reveals Hypermethylated Proteoforms from MMSET/NSD2 Overexpression. Molecular & cellular proteomics : MCP 62 26272979
2013 NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma. Cancer research 62 23980095
2018 High-throughput screening with nucleosome substrate identifies small-molecule inhibitors of the human histone lysine methyltransferase NSD2. The Journal of biological chemistry 60 29945974
2006 Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity. Biochemical and biophysical research communications 58 16682010
2009 The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription. FEBS letters 56 19481544
2011 MMSET is highly expressed and associated with aggressiveness in neuroblastoma. Cancer research 54 21527557
2021 Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2. Journal of medicinal chemistry 52 33522809
2021 NSD2 promotes tumor angiogenesis through methylating and activating STAT3 protein. Oncogene 52 33742125
2001 WHSC1L1, on human chromosome 8p11.2, closely resembles WHSC1 and maps to a duplicated region shared with 4p16.3. Genomics 50 11549311
2019 Histone methyltransferase NSD2 regulates apoptosis and chemosensitivity in osteosarcoma. Cell death & disease 49 30683853
2022 Melatonin enhances osteoblastogenesis of senescent bone marrow stromal cells through NSD2-mediated chromatin remodelling. Clinical and translational medicine 46 35220680
2016 Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36. Proceedings of the National Academy of Sciences of the United States of America 46 26787850
2018 An activating mutation of the NSD2 histone methyltransferase drives oncogenic reprogramming in acute lymphocytic leukemia. Oncogene 45 30171259
2023 Discovery of a Potent and Selective Targeted NSD2 Degrader for the Reduction of H3K36me2. Journal of the American Chemical Society 44 36976643
2024 Recruitment of FBXO22 for targeted degradation of NSD2. Nature chemical biology 43 38965384
2022 The role of NSD1, NSD2, and NSD3 histone methyltransferases in solid tumors. Cellular and molecular life sciences : CMLS 43 35532818
2021 Identification of histone methyltransferase NSD2 as an important oncogenic gene in colorectal cancer. Cell death & disease 41 34671018
2021 Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype. Genetics in medicine : official journal of the American College of Medical Genetics 40 33941880
2023 The location of the t(4;14) translocation breakpoint within the NSD2 gene identifies a subset of patients with high-risk NDMM. Blood 39 35984902
2001 A unique mRNA initiated within a middle intron of WHSC1/MMSET encodes a DNA binding protein that suppresses human IL-5 transcription. American journal of respiratory cell and molecular biology 38 11152655
2020 The NSD2/WHSC1/MMSET methyltransferase prevents cellular senescence-associated epigenomic remodeling. Aging cell 37 32573059
2020 The Role of Methyltransferase NSD2 as a Potential Oncogene in Human Solid Tumors. OncoTargets and therapy 37 32764971
2018 Developmental delay and failure to thrive associated with a loss-of-function variant in WHSC1 (NSD2). American journal of medical genetics. Part A 37 30345613
2004 Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma. British journal of haematology 37 15198734
2022 METTL3 enhances NSD2 mRNA stability to reduce renal impairment and interstitial fibrosis in mice with diabetic nephropathy. BMC nephrology 36 35354439
2019 Histone methyltransferase NSD2 mediates the survival and invasion of triple-negative breast cancer cells via stimulating ADAM9-EGFR-AKT signaling. Acta pharmacologica Sinica 36 30670815
2021 PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia. Cancer discovery 33 34417224
2017 MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 28512191
2012 The histone methyltransferase MMSET regulates class switch recombination. Journal of immunology (Baltimore, Md. : 1950) 33 23241889
2005 Evaluation of NSD2 and NSD3 in overgrowth syndromes. European journal of human genetics : EJHG 33 15483650
2021 Structural basis of the regulation of the normal and oncogenic methylation of nucleosomal histone H3 Lys36 by NSD2. Nature communications 32 34782608
2008 Identification of a novel proliferation-related protein, WHSC1 4a, in human gliomas. Neuro-oncology 32 18182627
2013 Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf-Hirschhorn Syndrome. European journal of human genetics : EJHG 31 23963300
2013 Plasma membrane proteomics identifies biomarkers associated with MMSET overexpression in T(4;14) multiple myeloma. Oncotarget 27 23900284
2022 H3K36me2 methyltransferase NSD2 orchestrates epigenetic reprogramming during spermatogenesis. Nucleic acids research 26 35736136
2020 Histone methyltransferase Nsd2 is required for follicular helper T cell differentiation. The Journal of experimental medicine 26 31636135
2018 De novo truncating variants in WHSC1 recapitulate the Wolf-Hirschhorn (4p16.3 microdeletion) syndrome phenotype. Genetics in medicine : official journal of the American College of Medical Genetics 26 29892088
2015 MMSET regulates expression of IRF4 in t(4;14) myeloma and its silencing potentiates the effect of bortezomib. Leukemia 26 26196464
2014 Histone H3 lysine 36 methyltransferase Whsc1 promotes the association of Runx2 and p300 in the activation of bone-related genes. PloS one 26 25188294
2023 Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2). Journal of medicinal chemistry 25 37578463
2024 NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis. Nature genetics 24 39251788
2016 Metformin Elicits Antitumor Effects and Downregulates the Histone Methyltransferase Multiple Myeloma SET Domain (MMSET) in Prostate Cancer Cells. The Prostate 24 27404348
2014 MMSET: role and therapeutic opportunities in multiple myeloma. BioMed research international 24 25093175
2019 De novo loss-of-function variants in NSD2 (WHSC1) associate with a subset of Wolf-Hirschhorn syndrome. Cold Spring Harbor molecular case studies 23 31171569
2017 DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites. The Journal of cell biology 23 29233865
2012 Overexpression of MMSET in endometrial cancer: a clinicopathologic study. Journal of surgical oncology 23 22886632
2022 Structure-Based Discovery of a Series of NSD2-PWWP1 Inhibitors. Journal of medicinal chemistry 22 35704853
2020 S-adenosylhomocysteine (AdoHcy)-dependent methyltransferase inhibitor DZNep overcomes breast cancer tamoxifen resistance via induction of NSD2 degradation and suppression of NSD2-driven redox homeostasis. Chemico-biological interactions 22 32001260
2019 Whsc1 links pluripotency exit with mesendoderm specification. Nature cell biology 22 31235934
2005 Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma. British journal of haematology 22 16197452
2023 All-trans retinoic acid improves NSD2-mediated RARα phase separation and efficacy of anti-CD38 CAR T-cell therapy in multiple myeloma. Journal for immunotherapy of cancer 21 36918219
2021 Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma. Oncogene 21 33420361
2021 Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2. Cell death discovery 21 33469000
2023 Recent advances in nuclear receptor-binding SET domain 2 (NSD2) inhibitors: An update and perspectives. European journal of medicinal chemistry 20 36863225
2021 SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic PTP4A3 through Chromatin Remodeling in t(4;14) Multiple Myeloma. Cancer research 20 33602783
2021 5-Aminonaphthalene derivatives as selective nonnucleoside nuclear receptor binding SET domain-protein 2 (NSD2) inhibitors for the treatment of multiple myeloma. European journal of medicinal chemistry 20 34147909
2023 Structural Modification and Pharmacological Evaluation of Substituted Quinoline-5,8-diones as Potent NSD2 Inhibitors. Journal of medicinal chemistry 19 36642961
2021 Circular RNA WHSC1 exerts oncogenic properties by regulating miR-7/TAB2 in lung cancer. Journal of cellular and molecular medicine 19 34551195
2020 H3K36 dimethylation by MMSET promotes classical non-homologous end-joining at unprotected telomeres. Oncogene 19 32472076
2019 NSD2 silencing alleviates pulmonary arterial hypertension by inhibiting trehalose metabolism and autophagy. Clinical science (London, England : 1979) 19 31040165
2020 WHSC1 Promotes Cell Proliferation, Migration, and Invasion in Hepatocellular Carcinoma by Activating mTORC1 Signaling. OncoTargets and therapy 18 32801739
2020 Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma. Molecular therapy. Nucleic acids 18 33552680
2015 Retinoic acid inhibits histone methyltransferase Whsc1 during palatogenesis. Biochemical and biophysical research communications 18 25677622
2024 Discovery of LLC0424 as a Potent and Selective in Vivo NSD2 PROTAC Degrader. Journal of medicinal chemistry 17 38687638
2019 Defining the NSD2 interactome: PARP1 PARylation reduces NSD2 histone methyltransferase activity and impedes chromatin binding. The Journal of biological chemistry 17 31248990
2018 MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells. Leukemia 17 30470837
2016 MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication. Cell cycle (Georgetown, Tex.) 17 26771714
2022 Histone methyltransferase Nsd2 ensures maternal-fetal immune tolerance by promoting regulatory T-cell recruitment. Cellular & molecular immunology 16 35322173
2020 NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling. Cancer management and research 16 32021450
2020 WHSC1 promotes wnt/β-catenin signaling in a FoxM1-dependent manner facilitating proliferation, invasion and epithelial-mesenchymal transition in breast cancer. Journal of receptor and signal transduction research 16 32314642
2019 Knockdown of NSD2 Suppresses Renal Cell Carcinoma Metastasis by Inhibiting Epithelial-Mesenchymal Transition. International journal of medical sciences 16 31692936
2005 Identification of ID-1 as a potential target gene of MMSET in multiple myeloma. British journal of haematology 15 16115125
2025 H3K36me2 methyltransferase NSD2/WHSC1 promotes triple-negative breast cancer metastasis via activation of ULK1-dependent autophagy. Autophagy 14 40097917
2024 Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation. Genome biology 14 39390582
2023 Histone Methyltransferase NSD2 Activates PKCα to Drive Metabolic Reprogramming and Lenalidomide Resistance in Multiple Myeloma. Cancer research 14 37463241