New publication in "ChemBioChem"
The SMYD2 protein lysine methyltransferase (PKMT) methylates different histone and non-histone proteins and it is overexpressed in several cancers. Using peptide arrays, we investigated the substrate specificity of the enzyme. Based on the specificity motif defined in our study, in total 32 novel peptide substrates of SMYD2 were discovered. Among them, 19 were already reported to be methylated at the target lysine in human cells, strongly suggesting that SMYD2 is the PKMT responsible for this activity. Methylation of the novel substrates was tested at the protein level leading to the identification of 14 novel protein substrates of SMYD2, 6 of which were more strongly methylated than p53, the best SMYD2 substrate described so far. The novel SMYD2 substrate proteins are involved in diverse processes like chromatin regulation, transcription and intracellular signaling. By this our study provides a fundament for future investigation of the role of this important enzyme in normal development and cancer.