PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation
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PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs. Our data also elucidate a major role of PARP9 and its binding partner, the E3 ubiquitin ligase DTX3L, in regulating PARP14 activity through protein-protein interactions and by the hydrolytic activity of PARP9 macrodomain 1. Finally, we also present the first visualisation of ADPr-dependent ubiquitylation in the IFN response. These approaches should further advance our understanding of IFN-induced ADPr and ubiquitin signalling processes and could shed light on how different pathogens avoid such defence pathways.
Original language | English |
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Journal | EMBO Journal |
Volume | 43 |
Issue number | 14 |
Pages (from-to) | 2929-2953 |
ISSN | 0261-4189 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© The Author(s) 2024.
- ADP-ribosylation, Immune Response, Interferon Response, SARS-CoV2, Ubiquitin
Research areas
ID: 394714476