Cell function is dependent upon protein covalent modifications that can serve as switches to regulate protein and gene activity and that can mark age-damaged proteins. These modifications can also create protein side chains with novel chemical and biochemical properties. Post-translational modifications range from single methyl groups to entire proteins (e.g., ubiquitin) that occur after a protein is translated from messenger RNA. These modifications expand the chemical properties of the twenty canonical amino acids encoded by the DNA, further diversifying the structure and function of the proteome. We are continuing our broad approach to delineate the physiological functions of these modifications, particularly those involved in cancer and aging.
Protein arginine methylation is a widespread post-translational modification in mammalian cells with suggested regulatory roles in cellular functions such as transcription, translation, cell signaling, DNA repair and protein stability. Protein arginine methyltransferases (PRMTs) modify peptidyl arginine residues by transferring methyl groups from S-adenosyl-L-methionine onto the ω-nitrogen atoms of the guanidino group of the arginine side chain.
As proteins age, they become damaged through the spontaneous racemization and isomerization of aspartic and asparaginyl residues. The accumulation of proteins with D- and isoAsp residues can result in loss of cell function.
Molecular aging is marked by the accumulation of covalently modified polypeptides. Survival during aging therefore depends in part on limiting the accumulation of proteins damaged by spontaneous chemical reactions to maintain homeostasis.
