The methylproteome and the intracellular methylation network

Since its discovery more than 50 years ago, post-translational modification (PTM) of proteins via methylation has grown in prominence, its involvement having been recognised in a number of central processes in the cell. Of these, the best characterised is its role in the epigenetic code. However, there is increasing evidence that its role extends far beyond this and we propose that it is a key regulator in interactome dynamics. In this review, we focus on the role of methylation in regulating protein-protein interactions and illustrate, by providing a broad-scale summary of our current knowledge of methylation and its impact on systems biology, how this can ultimately affect interactome dynamics. We describe the variety of analytical techniques available for the study of the methylproteome, comment on their advantages and limitations, and consider how these tools can help elucidate how methylation regulates the dynamics of the interactome. The insights gained from methyltransferase-substrate networks will be summarised and the ability of protein methylation to facilitate or block protein-protein interactions as well as their interplay with other post-translational modifications, in particular phosphorylation, is highlighted. Finally, the importance of methylation in pathology-associated protein interaction networks will be discussed using examples involving human diseases and the p53 protein.