Interplay between ubiquitination and ADP-ribosylation and the case of dual modification ADPr-Ub.

Abstract

Ubiquitination is a fundamental post-translational modification essential for nearly all cellular activities. Traditionally, ubiquitination has been understood as a protein modification, where ubiquitin (Ub) molecules are covalently attached to the lysine residues of substrate proteins, thereby modulating their function, localization, or degradation. However, recent discoveries have expanded the scope of ubiquitination beyond protein substrates. One of the examples is ubiquitination of ADP-ribose moieties on proteins or nucleic acids that leads to the formation of a dual-hybrid modification ADP-ribose-Ub (ADPr-Ub). This novel form of ubiquitination is catalyzed by Deltex ubiquitin ligases that act in concert with PARPs (Poly (ADP-ribose) polymerases), enzymes modifying their substrates by ADPr modification. This review summarizes our current knowledge of mechanisms and potential functional implications of ADPr-Ub. We also cover other examples of the interplay between ADP-ribosylation (ADPr) and ubiquitination beyond Deltex enzymes and ADPr-Ub.