Systems-wide analysis of serine-ADP-ribosylation reveals widespread occurrence and site-specific overlap with phosphorylation (part 2, phosphorylation data)

ABSTRACT: Here we report systems-wide identification of serine ADP-ribosylation sites and quantification of their cellular changes in human cells upon oxidative stress. High-resolution mass spectrometry and unrestricted data processing confirmed that serine residues are the major target of ADP-ribosylation in HeLa cells. Proteome-wide analyses identified 3,090 serine ADP-ribosylation sites, with 97 percent of acceptor sites modulated more than 2-fold upon oxidative stress, while treatment with PARP inhibitor Olaparib abrogates induction (part 1, ADP-ribosylation data, PXD009208). Consistent with the nuclear expression of ARTD1/PARP1 and ARTD2/PARP2, serine ADP-ribosylation prominently occurred on nuclear proteins. Structural-predictive analyses revealed that serine ADP-ribosylation preferentially resides in disordered regions, and identified serine ADP-ribosylation sites to significantly overlap with known phosphorylation sites. Large-scale phosphoproteomics analysis supported these observations (part 2, phosphorylation data), hereby providing first evidence for site-specific crosstalk between serine ADP-ribosylation and phosphorylation. Collectively, we demonstrate that serine ADP-ribosylation is a widespread modification and a major nuclear responder to oxidative stress, and that its regulatory scope is comparable to other posttranslational modifications.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Ivo Hendriks  

LAB HEAD: Michael Lund Nielsen

PROVIDER: PXD009931 | Pride | 2018-08-29

REPOSITORIES: Pride