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Updated: Jun 24, 2025

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PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation

Pulak Kar1,2, Chatrin Chatrin1, Nina Đukić1

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.

The EMBO Journal
|June 4, 2024
PubMed

Insights

Researchers developed new methods to study mono-ADP-ribosylation (ADPr), revealing PARP14

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Poly(ADP-ribose) polymerase (PARP)-catalyzed ADP-ribosylation (ADPr) regulates cellular processes.
  • PARP-dependent mono-ADP-ribosylation was previously difficult to study due to limited detection methods.

Purpose of the Study:

  • To develop and utilize sensitive methods for detecting mono-ADP-ribosylation.
  • To investigate the role of PARP enzymes in interferon (IFN)-induced signaling.
  • To explore the interaction between ADPr and ubiquitylation in the IFN response.

Main Methods:

  • Utilized an improved antibody for sensitive detection of mono-ADP-ribosylation.
  • Visualized endogenous IFN-induced ADP-ribosylation.
  • Investigated protein-protein interactions and enzymatic activities of PARP9, DTX3L, and SARS-CoV-2 Mac1.

Main Results:

  • Identified PARP14 as a key enzyme in IFN-induced ADP-ribosylation.
  • Demonstrated that SARS-CoV-2 Mac1 reverses PARP14-mediated signaling.
  • Elucidated the regulatory role of PARP9 and DTX3L in modulating PARP14 activity.
  • Visualized ADPr-dependent ubiquitylation in the IFN response for the first time.

Conclusions:

  • New methods advance the study of ADP-ribosylation and ubiquitylation in IFN signaling.
  • PARP14 is a crucial enzyme in IFN responses, targeted by viral factors like SARS-CoV-2 Mac1.
  • Understanding these pathways offers insights into pathogen evasion mechanisms.
Keywords:
ADP-ribosylationImmune ResponseInterferon ResponseSARS-CoV2Ubiquitin

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