Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation
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Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation. / Larsen, Sara C.; Hendriks, Ivo A.; Lyon, David; Jensen, Lars J.; Nielsen, Michael L.
I: Cell Reports, Bind 24, Nr. 9, 2018, s. 2493-2505.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation
AU - Larsen, Sara C.
AU - Hendriks, Ivo A.
AU - Lyon, David
AU - Jensen, Lars J.
AU - Nielsen, Michael L.
N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - ADP-ribosylation
KW - ADPr
KW - DNA damage
KW - mass spectrometry
KW - oxidative stress
KW - PARP inhibitor
KW - phosphorylation
KW - post-translational modification
KW - proteomics
KW - PTM
KW - serine ADP-ribosylation
U2 - 10.1016/j.celrep.2018.07.083
DO - 10.1016/j.celrep.2018.07.083
M3 - Journal article
C2 - 30157440
VL - 24
SP - 2493
EP - 2505
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
ER -
ID: 201913322