Please use this identifier to cite or link to this item:
Authors: Weirich, Sara
Kudithipudi, Srikanth
Kycia, Ina
Jeltsch, Albert
Title: Somatic cancer mutations in the MLL3-SET domain alter the catalytic properties of the enzyme
Issue Date: 2015 Zeitschriftenartikel Clinical epigenetics 7 (2015), Nr. 36. URL
Abstract: BACKGROUND: Somatic mutations in epigenetic enzymes are frequently found in cancer tissues. The MLL3 H3K4-specific protein lysine monomethyltransferase is an important epigenetic enzyme, and it is among the most recurrently mutated enzymes in cancers. MLL3 mainly introduces H3K4me1 at enhancers. RESULTS: We investigated the enzymatic properties of MLL3 variants that carry somatic cancer mutations. Asn4848 is located at the cofactor binding sites, and the N4848S exchange renders the enzyme inactive. Tyr4884 is part of an aromatic pocket at the active center of the enzyme, and Y4884C converts MLL3 from a monomethyltransferase with substrate preference for H3K4me0 to a trimethyltransferase with H3K4me1 as preferred substrate. Expression of Y4884C leads to aberrant H3K4me3 formation in cells. CONCLUSIONS: Our data show that different somatic cancer mutations of MLL3 affect the enzyme activity in distinct and opposing manner highlighting the importance of experimentally studying the effects of somatic cancer mutations in key regulatory enzymes in order to develop and apply targeted tumor therapy.
Appears in Collections:03 Fakultät Chemie

Files in This Item:
File Description SizeFormat 
s13148_015_0075_3_s1.pdfSupplemental figures361,5 kBAdobe PDFView/Open
Weirich_ClinEpi_2015.pdf2,72 MBAdobe PDFView/Open

Items in OPUS are protected by copyright, with all rights reserved, unless otherwise indicated.