Please use this identifier to cite or link to this item: http://dx.doi.org/10.18419/opus-10720
Authors: Weirich, Sara
Schuhmacher, Maren Kirstin
Kudithipudi, Srikanth
Lungu, Cristiana
Ferguson, Andrew D.
Jeltsch, Albert
Title: Analysis of the substrate specificity of the SMYD2 protein lysine methyltransferase and discovery of novel non-histone substrates
Issue Date: 2019
metadata.ubs.publikation.typ: Zeitschriftenartikel
metadata.ubs.publikation.seiten: 256-264
metadata.ubs.publikation.source: ChemBioChem 21 (2020), pp. 256-264
URI: http://elib.uni-stuttgart.de/handle/11682/10737
http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-107378
http://dx.doi.org/10.18419/opus-10720
ISSN: 1439-7633
1439-4227
Abstract: The SMYD2 protein lysine methyltransferase methylates various histone and non-histone proteins and is overexpressed in several cancers. Using peptide arrays, we investigated the substrate specificity of the enzyme, revealing a recognition of leucine (or weaker phenylalanine) at the -1 peptide site and disfavor of acidic residues at the +1 to +3 sites. Using this motif, novel SMYD2 peptide substrates were identified, leading to the discovery of 32 novel peptide substrates with a validated target site. Among them, 19 were previously reported to be methylated at the target lysine in human cells, strongly suggesting that SMYD2 is the protein lysine methyltransferase responsible for this activity. Methylation of some of the novel peptide substrates was tested at the protein level, leading to the identification of 14 novel protein substrates of SMYD2, six of which were more strongly methylated than p53, the best SMYD2 substrate described so far. The novel SMYD2 substrate proteins are involved in diverse biological processes such as chromatin regulation, transcription, and intracellular signaling. The results of our study provide a fundament for future investigations into the role of this important enzyme in normal development and cancer.
Appears in Collections:03 Fakultät Chemie

Files in This Item:
File Description SizeFormat 
Weirich_ChemBiochem_2020_Smyd2.pdfPaper1,25 MBAdobe PDFView/Open
smyd2_supporting_information.pdfSupporting information666,03 kBAdobe PDFView/Open


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