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.

In: Cell Reports, Vol. 24, No. 9, 2018, p. 2493-2505.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Larsen, SC, Hendriks, IA, Lyon, D, Jensen, LJ & Nielsen, ML 2018, 'Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation', Cell Reports, vol. 24, no. 9, pp. 2493-2505. https://doi.org/10.1016/j.celrep.2018.07.083

APA

Larsen, S. C., Hendriks, I. A., Lyon, D., Jensen, L. J., & Nielsen, M. L. (2018). Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation. Cell Reports, 24(9), 2493-2505. https://doi.org/10.1016/j.celrep.2018.07.083

Vancouver

Larsen SC, Hendriks IA, Lyon D, Jensen LJ, Nielsen ML. Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation. Cell Reports. 2018;24(9):2493-2505. https://doi.org/10.1016/j.celrep.2018.07.083

Author

Larsen, Sara C. ; Hendriks, Ivo A. ; Lyon, David ; Jensen, Lars J. ; Nielsen, Michael L. / Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation. In: Cell Reports. 2018 ; Vol. 24, No. 9. pp. 2493-2505.

Bibtex

@article{61425bbccaf54284b7090861fe6bac90,
title = "Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation",
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.",
keywords = "ADP-ribosylation, ADPr, DNA damage, mass spectrometry, oxidative stress, PARP inhibitor, phosphorylation, post-translational modification, proteomics, PTM, serine ADP-ribosylation",
author = "Larsen, {Sara C.} and Hendriks, {Ivo A.} and David Lyon and Jensen, {Lars J.} and Nielsen, {Michael L.}",
note = "Copyright {\circledC} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.celrep.2018.07.083",
language = "English",
volume = "24",
pages = "2493--2505",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",

}

RIS

TY - JOUR

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