PARP14 and PARP9/DTX3L Regulate Interferon-induced ADP-ribosylation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2024 Jun 4

PMID 38834853

Authors

Pulak Kar

Chatrin Chatrin

Nina dukic

Osamu Suyari

Marion Schuller

Kang Zhu

Evgeniia Prokhorova

Nicolas Bigot

Domagoj Baretic

Juraj Ahel

Jonas Damgaard Elsborg

Michael L Nielsen

Tim Clausen

Sebastien Huet

Mario Niepel

Sumana Sanyal

Dragana Ahel

Rebecca Smith

Ivan Ahel

Affiliations

Soon will be listed here.

Abstract

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.

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