The Promise of Proteomics for the Study of ADP-Ribosylation

Casey M. Daniels, Shao En Ong, Anthony Kar Lun Leung

Research output: Contribution to journalReview article

Abstract

ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death. Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials. The study of this therapeutically important modification has recently been bolstered by the application of mass spectrometry-based proteomics, arguably the most powerful tool for the unbiased analysis of protein modifications. Unfortunately, progress has been hampered by the inherent challenges that stem from the physicochemical properties of ADP-ribose, which as a post-translational modification is highly charged, heterogeneous (linear or branched polymers, as well as monomers), labile, and found on a wide range of amino acid acceptors. In this Perspective, we discuss the progress that has been made in addressing these challenges, including the recent breakthroughs in proteomics techniques to identify ADP-ribosylation sites, and future developments to provide a proteome-wide view of the many cellular processes regulated by ADP-ribosylation.

Original languageEnglish (US)
Pages (from-to)911-924
Number of pages14
JournalMolecular Cell
Volume58
Issue number6
DOIs
StatePublished - Jun 18 2015

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Proteomics
Adenosine Diphosphate
Post Translational Protein Processing
ADP Ribose Transferases
Adenosine Diphosphate Ribose
Proteome
DNA Repair
Neurodegenerative Diseases
Mass Spectrometry
Polymers
Proteins
Cell Death
Heart Failure
Clinical Trials
Amino Acids
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

The Promise of Proteomics for the Study of ADP-Ribosylation. / Daniels, Casey M.; Ong, Shao En; Leung, Anthony Kar Lun.

In: Molecular Cell, Vol. 58, No. 6, 18.06.2015, p. 911-924.

Research output: Contribution to journalReview article

Daniels, Casey M. ; Ong, Shao En ; Leung, Anthony Kar Lun. / The Promise of Proteomics for the Study of ADP-Ribosylation. In: Molecular Cell. 2015 ; Vol. 58, No. 6. pp. 911-924.
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