PAD: the smoking gun behind arginine methylation signaling?

Post-translational modifications (PTM) supply the proteome with functional and regulatory diversity. Modifications including phosphorylation, acetylation and methylation have been identified in eucaryotic proteins. For all but the last, corresponding "de-modifying" enzymes exist to remove the PTM tag returning the protein to its basal state. Recently, a novel mechanism in which peptidylarginine deiminase (PAD4) converts histone H3 and H4 methyl arginine residues into citrulline was proposed to regulate estrogen-responsive gene transcription.1,2 These data, the first to provide a mechanistic basis for the dynamic changes observed in a subset of protein arginine methylated substrates,3 lead to a host of questions concerning the generality of this mechanism for non-histone targets of the protein arginine methyltransferases (PRMTs).