2020
DOI: 10.1101/gad.334425.119
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The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

Abstract: Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD+ to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host–pathogen interactions. Here … Show more

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Cited by 179 publications
(210 citation statements)
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“…When IFN binds to its receptor, the IFN α/β receptor (IFNAR), it initiates a signaling cascade that results in the transcription of hundreds of interferon-stimulated genes (ISGs), many of which have antiviral activities. PARPs have many well-known pro-and antiviral activities (reviewed in Reference [16]). For instance, PARP12 is required for the ADP-ribosylation of Zika virus proteins NS1 and NS3 that inhibit Zika virus replication [17].…”
Section: Adp-ribosylation and The Innate Immune Responsementioning
confidence: 99%
“…When IFN binds to its receptor, the IFN α/β receptor (IFNAR), it initiates a signaling cascade that results in the transcription of hundreds of interferon-stimulated genes (ISGs), many of which have antiviral activities. PARPs have many well-known pro-and antiviral activities (reviewed in Reference [16]). For instance, PARP12 is required for the ADP-ribosylation of Zika virus proteins NS1 and NS3 that inhibit Zika virus replication [17].…”
Section: Adp-ribosylation and The Innate Immune Responsementioning
confidence: 99%
“…PARP enzymes have widespread biological functions ranging from DNA repair and chromatin structure (Javle and Curtin 2011;De Vos et al 2012;Dantzer and Santoro 2013), RNA transcription, protein translation, and degradation (Kraus and Hottiger 2013;Bai 2015), cell division, tumor biology (Curtin and Szabo 2013), immune processes (Fehr et al 2020) metabolism, and mitochondrial biology (Bai and Cantó 2012;, oxidative stress biology, and cell death and differentiation, and aging (Mangerich et al 2010;Burkle and Virag 2013;Fatokun et al 2014). In this review, we focus on the metabolic properties of PARP enzymes.…”
Section: Brief Introduction To Adp-ribose Metabolismmentioning
confidence: 99%
“…In this work we stress the fact that besides the replicative and structural proteins, all of which are critical for the viral cycle, other proteins also have vital functions, and thus would constitute excellent targets for drug discovery. The helicase (nsp13), and methyl-transferases N7-Mtase (nsp14) and 2′-O-MTase (nsp16) contribute to genome stability through their involvement in the capping process; the ExoN (nsp14) is responsible for proofreading, and thus for the extremely low mutation rate and nucleoside analogs resistanse of SARS-CoV-2; several nsp3 domains, such as SUD, NAB and Ub1 are known to bind ssRNA; the NendoU (nsp15) cleaves polyuridines produced during the priming of the poly(A) ssRNA during replication, which helps to dampen dsRNA MDA5-dependent antiviral IFN responses [125]; nsp9 acts as a hub that binds ssRNA and interacts with nsp8, the N protein, and several host nuclear pore proteins [15,130,131]; the ADRP and PL pro attenuate the effects of IFN and cytokine signaling components that induce antiviral and inflammatory responses [54,142]; orf3a and orf7a induce NFB, IL-8, and JNK, promoting inflammatory responses [198], while orf3a also induces the production of fibrinogen, promoting fibrosis, one of the complications of COVID-19 [197]; orf9b is involved in suppressing mitochondrial mediated IFN antiviral responses [210]; orf6 is known to increase the lethality in CoVs by enhancing viral replication and inhibiting IFN signaling [220,223]. In CoVs, a delayed IFN response is a redundant pattern that allows robust viral replication, and also induces the accumulation of cytokine-producing macrophages, thus increasing the severity of the disease [228].…”
Section: Discussion and Perspectivementioning
confidence: 99%
“…This appears to be related to the removal of ADP-ribose from ADP-ribosylated proteins or nucleic acids (RNA and DNA); it should be pointed out that ADRP is able to remove mono-ADP-ribose, but not poly-ADP-ribose [141]. Anti-viral ADP-ribosylation is a host post-translational modification in response to viral infections, since many of the IFN and cytokine signaling components, as NF-kappa-B essential modulator (NEMO), TANK-binding kinase 1 (TBK1), NFB among others need to be ribosilated to be fully active [142,143]. Although ADRP is not an essential protein for viral replication, it has been shown to be an essential pathogenesis factor in animal models for CoV infection; for example, mutations of ADRP in SARS-CoV enhanced IFN response and reduced viral loads in vivo in mice models [144,145].…”
Section: Adp-ribose-phosphatase (Nsp3 Domain)mentioning
confidence: 99%