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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
Summary
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.
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