New research project at IBC

April 9, 2015 / Albert Jeltsch

Somatic cancer mutations in PKMTs

Functional analysis of somatic cancer mutations in protein lysine methyltransferases (PKMTs)

Methylation of lysine residues is an important post-translational modification of histone and non-histone proteins, which is introduced by protein lysine methyltransferases (PKMTs). Recently, somatic mutations in PKMTs were discovered in various tumors. Here, we plan to investigate the mechanism of such somatic cancer mutations in important PKMTs in vitro and in cells. We will study the influence of the mutations on central enzymatic properties of the PKMTs: 1) The amino acid sequence substrate specificity, which determines the potential of PKMTs to methylate various different substrates. 2) The influence of existing methylation on the target lysine, which determines the dependence on other PKMTs. 3) Whether mono-, di-, or trimethylated lysine is generated as product, which determines the biological effect of the lysine methylation. 4) If the PKMT mutations alter the proliferation of cells. 5) The effect of known PKMT inhibitors on selected PKMT cancer mutants. Our data will help to understand the carcinogenic mechanism of PKMT mutations and PKMTs in general and develop individualized cancer therapies.

The project is supported by the Sander Foundation.

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