Abstract
ADP-ribosylation (ADPr) is a reversible posttranslational modification involved in a range of cellular processes. Here, we report system-wide identification of serine ADPr in human cells upon oxidative stress. High-resolution mass spectrometry and unrestricted data processing confirm that serine residues are the major target of ADPr in HeLa cells. Proteome-wide analysis identifies 3,090 serine ADPr sites, with 97% of acceptor sites modulating more than 2-fold upon oxidative stress, while treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib abrogates this induction. Serine ADPr predominantly targets nuclear proteins, while structural-predictive analyses reveal that serine ADPr preferentially targets disordered protein regions. The identified ADP-ribosylated serines significantly overlap with known phosphorylated serines, and large-scale phosphoproteomics analysis provides evidence for site-specific crosstalk between serine ADPr and phosphorylation. Collectively, we demonstrate that serine ADPr is a widespread modification and a major nuclear signaling response to oxidative stress, with a regulatory scope comparable to other extensive posttranslational modifications.
| Original language | English |
|---|---|
| Journal | Cell Reports |
| Volume | 24 |
| Issue number | 9 |
| Pages (from-to) | 2493-2505 |
| ISSN | 2211-1247 |
| DOIs | |
| Publication status | Published - 2018 |
Keywords
- ADP-ribosylation
- ADPr
- DNA damage
- mass spectrometry
- oxidative stress
- PARP inhibitor
- phosphorylation
- post-translational modification
- proteomics
- PTM
- serine ADP-ribosylation