Recombinant Human Probable histone-lysine N-methyltransferase NSD2 (WHSC1), partial

1. Mutations in NSD1 or NSD2 are independent favorable prognostic biomarkers for laryngeal cancer. PMID: 29176703
2. The MMSET is required for efficient NER and that it catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2). PMID: 29233865
3. NSD2 promoted the proliferation of pancreatic beta cell lines. Moreover, ectopic expression of NSD2 significantly promoted insulin secretion. In addition, NSD2 served as a transfection factor and it was identified that NSD2 transcriptionally regulated PDX1 expression through its H3K36me2 methyltransferase activity. PMID: 30066931
4. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays. Furthermore, a crystal structure was solved with the peptide in complex with SAM and the SET domain of WHSC1L1 PMID: 29742153
5. The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. PMID: 27604143
6. MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. PMID: 26847058
7. These findings indicate that the miR-2392-MAML3/WHSC1-Slug/Twist1 regulatory axis plays a critical role in GC metastasis. PMID: 28512191
8. In a murine xenograft model using t(4;14)+ KMS11 MM cells harboring an inducible MMSET shRNA, depletion of MMSET enhanced the efficacy of chemotherapy, inhibiting tumor growth and extending survival. PMID: 27109101
9. data suggest multiple myeloma SET domain containing protein(MMSET) may play a role in the inhibitory effect of metformin on prostate cancer and could serve as a potential novel therapeutic target for prostate cancer PMID: 27404348
10. NSD2 overexpression is significantly associated with high risk of relapse and poor survival in tamoxifen-treated ER-positive breast cancer patients via coordinated activation of pentose phosphate pathway enzymes. PMID: 27164560
11. Results show that WHSC1 is hypomethylated in cervical cancer cells and tissues. Both methylation and mRNA expression of WHSC1 were significantly correlated with lymph node metastasis and the overall survival of patients. PMID: 28260054
12. Results showed that high levels of MMSET in the myeloma-like cells drove the formation of hypermethyled proteoforms containing H3K36me2 co-existent with the repressive marks H3K9me2/3 and H3K27me2/3. PMID: 26272979
13. In MMSET-depleted cells there are defects in DNA replication and a decreased association with chromatin. PMID: 26771714
14. results identify a pivotal role for NSD2 binding to its catalytic product in regulating its cellular functions, and suggest a model for how this interaction may facilitate epigenetic spreading and propagation of H3K36me2. PMID: 26912663
15. NSD2 preferentially catalyzes the dimethylation of H3K36 along with a reduced preference for H3K36 monomethylation PMID: 26787850
16. Studies indicate that the NSD methyltransferases NSD1, NSD2/WHSC1/MMSET and NSD3/WHSC1L1 were overexpressed, amplified or somatically mutated in multiple types of cancer, suggesting their critical role in cancer. PMID: 25942451
17. It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. PMID: 26206755
18. Results show that WHSC1 is overexpressed in Squamous cell carcinoma of the head and neck (SCCHN) and that it promotes cell-cycle progression through activation of NEK7, indicating its potential role as an oncogenic force in SCCHN. PMID: 25280969
19. The results describe the binding of NSD1, 2 and 3 catalytic domains (CD) on histone tails through recognition of histone-lysine and methylation properties. PMID: 25494638
20. The role of the shorter isoform (REIIBP) in myeloma cells was characterized and identified a clear and novel interaction of REIIBP with members of the SMN complex. PMID: 24923560
21. Haploinsufficiency of WHSC1 and/or LETM1 contributes to Wolf-Hirschhorn Syndrome, but that loss of distinct and/or additional genes in 4p16.3 is necessary for the expression of the core Wolf-Hirschhorn Syndrome phenotype. PMID: 23963300
22. Gastric cancer patients with high MMSET and BRCA1 attain a longer median survival compared with those with high BRCA1 and low MMSET. PMID: 24809779
23. In this study it was found MMSET knockdown could reduce SLAMF7 levels in t(4;14) MM cells. Furthermore, we found MMSET proteins were enriched in the SLAMF7 promoter region and regulated the transcription level of SLAMF7. PMID: 23900284
24. it will be of interest to determine whether inhibition of MMSET activity can be beneficial not only for t(4;14)thorn MM patients but also for patients who express a mutant allele of this protein. PMID: 23823660
25. Overexpression of MMSET was significantly associated with Edmondson stage. PMID: 23225158
26. all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A. PMID: 24019522
27. High MMSET expression correlated with the advanced extent of serous ovarian carcinoma and poor outcome. PMID: 23566000
28. Depletion of TWIST1 in MMSET-overexpressing cells blocked cell invasion and epithelial-mesenchymal transition, indicating that TWIST1 is a critical target of MMSET, responsible for the acquisition of an invasive phenotype. PMID: 22797064
29. Overexpression of the histone methyltransferase MMSET is associated with myeloma. PMID: 22972034
30. MMSET, a gene often deleted in Wolf-Hirschhorn syndrome, regulates class switch recombination provides one possible mechanism for Ab deficiency observed in these patients. PMID: 23241889
31. The EZH2-MMSET-histone methylase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis. PMID: 23159737
32. ACA11, an orphan box H/ACA class small nucleolar RNA (snoRNA) encoded within an intron of WHSC1, was highly expressed in t(4;14)-positive multiple myeloma and other cancers PMID: 22751105
33. NSD2 is a key chromatin regulator of NF-kappaB and mediator of the cytokine autocrine loop for constitutive NF-kappaB activation and emphasize the important roles played by NSD2 in cancer cell proliferation and survival and tumor growth. PMID: 22645312
34. Data show significant up-regulation of WHSC1 expression in bladder and lung cancer cells at both transcriptional and the protein levels. PMID: 22028615
35. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. PMID: 22099308
36. WHSC1 regulates the methylation status of the histone H4 K20 residue and is required for the recruitment of 53BP1 to sites of DNA damage. PMID: 21788515
37. The histone methyltransferase and putative oncoprotein MMSET is overexpressed in a large variety of human tumors. PMID: 21385930
38. MMSET is implicated in neuroblastomagenesis possibly by supporting proliferation of progenitor cells and negatively regulating their differentiation. PMID: 21527557
39. overexpression of multiple myeloma SET domain protein is associated with the translocation t(4;14)in multiple myeloma. PMID: 20974671
40. a pathway involving gammaH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment PMID: 21293379
41. data indicate that t(4;14)(p16;q32) and loss of fibroblast growth factor receptor 3 occurred at a very early stage of multiple myeloma and suggest that activation of multiple myeloma SET domain protein may be transforming event of this translocation PMID: 12433679
42. connection between the syndrome phenotype and cytogenetic abnormalities, through gradual shortening of the length of the critical region WHSCR (finally up to 165 kb), and sequencing it, at least 2 genes (WHSC1 and WHSC2) were identified. PMID: 12715353
43. different transcripts detected, multiple myeloma SET domain containing protein (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein (RE-IIBP), are produced by alternative splicing PMID: 15677557
44. Overexpression of WHISTLE repressed transcription of the SV40 promoter. Our results suggest that WHISTLE is a novel SET domain containing a protein with specific H3K4 and H3K27 HMTase activity. PMID: 16682010
45. Our results suggest that HMTase WHISTLE induces apoptosis in an HMTase activity-dependent manner and represses transcription of target genes through HDAC1 recruitment. PMID: 17239852
46. that MMSET plays a significant role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients. PMID: 17942756
47. MM Patients showing the t(4;14) chromosomal translocation at FGFR3 and MMSET genes had a significant elevation of serum crosslaps, reported to be the marker most reliably correlated with the extent of bone resorption PMID: 18036184
48. MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma PMID: 18156491
49. RE-IIBP is upregulated in leukemia. SET domain Cys483 & Arg477 are needed for histone methyltransferase activity. Overexpression causes histone H3-K27 methylation, HDAC recruitment, & histone H3 hypoacetylation on the IL-5 promoter repressing expression. PMID: 18172012
50. WHSC1 expression increases with ascending tumor proliferation activity. PMID: 18182627

显示更多

收起更多

HGNC: 12766

OMIM: 602952

KEGG: hsa:7468

STRING: 9606.ENSP00000372347

UniGene: Hs.113876