Systems-wide Analysis of Serine ADP-Ribosylation Reveals Widespread Occurrence and Site-Specific Overlap with Phosphorylation

Cell Reports
Sara C LarsenMichael L Nielsen

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.

Citations

Apr 18, 2019·Open Biology·Luca PalazzoIvan Ahel
Feb 25, 2019·Molecular & Cellular Proteomics : MCP·Ivo A HendriksMichael L Nielsen
Aug 16, 2019·Cells·Ann-Katrin HoppMichael O Hottiger
Feb 8, 2020·Genes & Development·Kameron Azarm, Susan Smith
Feb 8, 2020·Genes & Development·Johannes Gregor Matthias RackIvan Ahel
Sep 18, 2020·Nature·Silvija BilokapicMario Halic
Feb 6, 2020·Cell & Bioscience·Muzaffer Ahmad KassabXiaochun Yu
Aug 14, 2020·The FEBS Journal·Marcin J SuskiewiczIvan Ahel
Feb 3, 2019·Biochemical Society Transactions·Giovanna Grimaldi, Daniela Corda
Feb 26, 2019·Nucleic Acids Research·Elizaveta E Alemasova, Olga I Lavrik
Jul 10, 2020·Cancers·Marina Engbrecht, Aswin Mangerich
Oct 9, 2020·Signal Transduction and Targeted Therapy·Na XieBingwen Zou
Nov 3, 2020·Nucleic Acids Research·Vinay AyyappanAnthony K L Leung
Jan 8, 2021·Molecular Cell·Marie-Michelle GenoisLee Zou
May 1, 2019·Molecular & Cellular Proteomics : MCP·Ivo A HendriksMichael L Nielsen
Jan 16, 2021·Molecular Cell·Ann-Katrin HoppMichael O Hottiger
Sep 24, 2020·Cell Reports·Sara C Buch-LarsenMichael L Nielsen
Jun 3, 2021·International Journal of Molecular Sciences·Lotte van BeekTaiana Maia de Oliveira
Jun 12, 2021·DNA Repair·Joséphine GroslambertIvan Ahel
Jun 26, 2021·Nature Communications·Rebecca GupteW Lee Kraus
Aug 3, 2021·Current Opinion in Genetics & Development·Luca PalazzoIvan Ahel
Jun 13, 2020·Journal of Proteome Research·Casey M DanielsAleksandra Nita-Lazar
Nov 4, 2020·Journal of the American Society for Mass Spectrometry·Peter M GehrigMichael O Hottiger
Aug 16, 2021·Pharmacology & Therapeutics·Zsofia Lengyel-ZhandRobert H Mach
Aug 26, 2021·Nature Reviews. Molecular Cell Biology·Ji-Hoon Lee, Tanya T Paull
Dec 21, 2019·Journal of Proteome Research·Robert Lyle McPhersonAnthony K L Leung
Oct 10, 2021·Nature Communications·Ivo A HendriksMichael L Nielsen
Oct 15, 2021·ACS Chemical Biology·Sean R WallaceIan Carter-O'Connell
Jul 3, 2021·Nature Communications·Evgeniia ProkhorovaIvan Ahel
Jan 15, 2022·Nature Communications·Julien BrustelNicholas D Lakin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.