Mutant human recombinant NSD2 with lysine (K) substituted for glutamate-1099 (E1099). Catalyzes the transfer of methyl groups from S-adenosyl-L-methionine (SAM) to the e-amino function of protein L-lysine residues, specifically lysine-36 of histone H3 (H3K36)1 (see also review2). H4K20 methylation by NSD2 may be linked to double strand breaks and the DNA damage response3, whereas its principal regulatory functions appear to occur via methylation of H3K364,5, a mark associated with active transcription. NSD2 is overexpressed in multiple myelomas with the t(4;14) translocation6. NSD2 knockdown in such cells induces apoptosis4, while overexpression of catalytically active NSD2 promotes oncogenic transformation and tumor formation even in the absence of the translocation5. In addition to t(4;14)+ multiple myelomas, NSD2 expression is elevated in a variety of cancers (bladder7,8, breast7, prostate7, kidney7, lung7,8, pancreas7, colon8, stomach8, anal canal8, female genitals8, skin8, neuroblastoma9) and its carcinogenic effects may be mediated by interaction with ß-catenin and effects on the WNT pathway7. Like cells in which translocations drive NSD2 overexpression, tumor lines bearing an NSD2-E1099K mutant allele display elevated levels of H3K36 dimethylation.10,11 A truncated, SET-domain E1099K construct (residues 955-1365) has been reported to exhibit higher methylation activity toward nucleosomes in vitro.11 Although observed in other cancers, the E1099K mutation appears to be most prevalent in pediatric acute lymphoblastic leukemia (ALL), the most common childhood cancer.10,11 Knockdown of NSD2-E1099K in ALL lines.
ACCESSION #: NM_001042424
INCLUDES AMINO ACIDS: 934-1241; contains wild-type residues 934-1098, 1100-1241
TAG(S): N-terminal His-tag
MW: 37.4 kDa
EXPRESSION SYSTEM: E. coli
SUPPLIED AS: µM NSD2-E1099K-SET (__ µg/µl total protein) in 50 mM Tris/HCl pH 7.5, 500 mM NaCl, 1 mM TCEP, 10% glycerol (v/v).
STORAGE: -70°C. Thaw quickly and store on ice before use. The remaining, unused, undiluted enzyme should be snap frozen, for example in a dry/ice ethanol bath or liquid nitrogen. Minimize freeze/thaws if possible, but very low volume aliquots (<5 µl) or storage of diluted enzyme is not recommended.
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