Protein lysine methylation is a functionally diverse post-translational modification involved
in various major cellular processes. Lysine methylation can modulate proteins activity, stability, localization,
and/or interaction, resulting in specific downstream signaling and biological outcomes. Lysine
methylation is a dynamic and fine-tuned process, deregulation of which often leads to human pathologies.
In particular, the lysine methylome and its associated signaling network can be linked to carcinogenesis
and cancer progression.
Histone modifications and chromatin regulation is a major aspect of lysine methylation importance, but
increasing evidence suggests that a high relevance and impact of non-histone lysine methylation signaling
has emerged in recent years. In this review, we draw an updated picture of the current scientific
knowledge regarding non-histone lysine methylation signaling and its implication in physiological and
pathological processes. We aim to demonstrate the significance of lysine methylation as a major and
yet underestimated posttranslational modification, and to raise the importance of this modification in
both epigenetic and cellular signaling by focusing on the observed activities of SET- and 7β-strandcontaining
human lysine methyltransferases.
Recent evidence suggests that what has been observed so far regarding lysine methylation’s implication
in human pathologies is only the tip of the iceberg. Therefore, the exploration of the “methylome
network” raises the possibility to use these enzymes and their substrates as promising new therapeutic
targets for the development of future epigenetic and methyllysine signaling cancer treatments.