ADP-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control

Among the post-translational modifications of proteins, ADP-ribosylation has been studied for over fifty years, and a large set of functions, including DNA repair, transcription, and cell signaling, have been assigned to this post-translational modification (PTM). This review presents an update on the function of a large set of enzyme writers, the readers that are recruited by the modified targets, and the erasers that reverse the modification to the original amino acid residue, removing the covalent bonds formed. In particular, the review provides details on the involvement of the enzymes performing monoADP-ribosylation/polyADP-ribosylation (MAR/PAR) cycling in cancers. Of note, there is potential for the application of the inhibitors developed for cancer also in the therapy of non-oncological diseases such as the protection against oxidative stress, the suppression of inflammatory responses, and the treatment of neurodegenerative diseases. This field of studies is not concluded, since novel enzymes are being discovered at a rapid pace.

Automated summary

ADP-ribosylation plays a crucial role in post-translational modifications of proteins, involving functions such as DNA repair, transcription, and cell signaling. Enzymes involved in monoADP-ribosylation/polyADP-ribosylation (MAR/PAR) cycling also play important roles in cancers, with potential applications in non-oncological diseases. The field is still actively uncovering novel enzymes at a rapid pace.