Reversal of tyrosine-linked ADP-ribosylation by ARH3 and PARG
ADP-ribosylation is an ancient posttranslational modification with exceptional versatility in terms of breadth of modification targets including at least seven different amino acid side chains, various moieties on nucleic acids, and a variety of small chemical compounds. The spatiotemporal signaling dynamic of the different modification variations is tightly regulated and depends on the writers, erases, and readers of each type. Among these, tyrosine ADP-ribosylation (Tyr-ADPr) has been consistently detected as a novel modification type, but systematic analysis of its potential physiological role, modification establishment, and reversal are still lacking. Here we present a re-analysis of recent ADP-ribosylome data and show that Tyr-ADPr sites are conserved and enriched among ribosome biogenesis and mRNA processing proteins and that these sites are affected by the status of the (ADP-ribosyl)hydrolase ARH3. To facilitate the study of Tyr-ADPr, we establish methodologies for the synthesis of well-defined Tyr-ADPr peptides and with these could show that Tyr-ADPr is reversed both by ARH3 and PARG enzymes. Together, our work lays the foundation for the future exploration of the Tyr-ADPr.
Authors
- Alessandra Peters (ORCID: https://orcid.org/0000-0001-9334-2568)
- Edoardo José Longarini (ORCID: https://orcid.org/0000-0003-3919-1169)
- Ivan Ahel
- Dragana Ahel (ORCID: https://orcid.org/0000-0002-7042-156X)
- Ivan Matić (ORCID: https://orcid.org/0000-0003-0170-7991)
- J.G.M. Rack (ORCID: https://orcid.org/0000-0001-8341-6439)
- Sven Wijngaarden (ORCID: https://orcid.org/0000-0002-6449-4113)
- Jim Voorneveld
- Evgeniia Prokhorova (ORCID: https://orcid.org/0000-0002-5467-5586)
- Kang Zhu (ORCID: https://orcid.org/0000-0003-2623-3331)
- Dmitri V. Filippov (ORCID: https://orcid.org/0000-0002-6978-7425)
- Jia Jhing Sia
Institutions
- Leiden University (NL)
- University of Applied Sciences Leiden (NL)
- University of Exeter (GB)
- University of Oxford (GB)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Max Planck Institute for Biology of Ageing (DE)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1016/j.jbc.2024.107838
- Citations
- 10
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 2.83
Funders
- Wellcome Trust
- Ovarian Cancer Research Fund Alliance
- Ovarian Cancer Research Alliance
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- University of Exeter
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- Medical Research Council Centre for Medical Mycology
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- H2020 European Research Council