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.