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Deciphering ADP-ribosylation signalling

Nature Reviews Molecular Cell Biology volume 25, page 3 (2024)Cite this article

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Post-translational modifications (PTMs) of proteins are key modulators of cellular signalling pathways and development of antibodies against PTMs has enabled transformative discoveries. ADP ribosylation (ADPr) uses NAD+ as ADP-ribose donor and is involved in many biological processes and diseases, such as viral infections, neurodegeneration, DNA damage repair, and cancer. ADPr can result in a single ADP-ribose modification (mono-ADPr), or in polymerization of ADP-ribose chains of up to ~200 units (poly-ADPr). Owing to lack of research tools such as antibodies and peptides, the study of ADPr has lagged behind that of other PTMs.

To overcome this technical gap, we sought to develop a method that would enable the generation of site-specific modified peptides, both for antibody development and as standalone tools. We capitalized on the discovery by our laboratory of Ser ADPr, transforming its writer complex into a tool for the preparation of ADPr peptides. However, the PARP1–HPF1 complex has low selectivity and thus modifies off-target Ser residues. To overcome this limitation, we harnessed the biological interplay between phosphorylation and ADPr, which enabled us to protect off-target Ser residues from ADPr by phosphorylating them.

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References

Original articles

  • Bonfiglio, J. J. et al. An HPF1/PARP1-based chemical biology strategy for exploring ADP-ribosylation. Cell 183, 1086–1102 (2020)

    Article  CAS  PubMed  Google Scholar 

  • Longarini, E. J. et al. Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling. Mol. Cell 83, 1743–1760 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Research Group of Proteomics and ADP-ribosylation Signalling, Max Planck Institute for Biology of Ageing, Cologne, Germany

    Edoardo José Longarini & Helen Dauben

Authors
  1. Edoardo José Longarini
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  2. Helen Dauben
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Both authors contributed equally to this work.

Corresponding authors

Correspondence to Edoardo José Longarini or Helen Dauben.

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Competing interests

The authors declare that Max-Planck-Innovation, the technology transfer centre of the Max Planck Society, has licensed the antibody AbD43647 to Bio-Rad Laboratories.

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Longarini, E.J., Dauben, H. Deciphering ADP-ribosylation signalling. Nat Rev Mol Cell Biol 25, 3 (2024). https://doi.org/10.1038/s41580-023-00630-x

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