Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose.

ABSTRACT: The prevailing view on post-translational modifications (PTMs) is that a single amino acid is modified with a single PTM at any given time. However, recent work has demonstrated crosstalk between different PTMs, some occurring on the same residue. Such interplay is seen with ADP-ribosylation and ubiquitylation. For example, DELTEX E3 ligases were reported to ubiquitylate a hydroxyl group on free NAD⁺ and ADP-ribose in vitro, generating a noncanonical ubiquitin ester-linked species. In this report, we show, for the first time, that this dual PTM occurs in cells on mono-ADP-ribosylated (MARylated) PARP10 on Glu/Asp sites to form a MAR ubiquitin ester. We call this process mono-ADP-ribosyl ubiquitylation or MARUbylation. Using chemical and enzymatic treatments, including a newly ch

SUBMITTER: Bejan DS 

PROVIDER: S-EPMC12000418 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature