ADPriboDB: The database of ADP-ribosylated proteins

Vivelo, Christina A.; Wat, Ricky; Agrawal, Charul; Tee, Hui Yi; Leung, Anthony K.L.

doi:10.1093/nar/gkw706

Cited by 58 publications

(43 citation statements)

References 52 publications

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“…iBAQ analysis of proteins identified in (A) is plotted as the log 2 value of the enrichment ratio (mass spectrometry intensity of the HALO-NEDP1 CA pulldown over HALO-NEDP1 DAGC pulldown) versus the log 10 value of the iBAQ intensity from the HALO-NEDP1 CA pulldown. Blue markers indicate known components of the NEDD8 pathway, and red markers indicate proteins that have been identified as substrates of PARP-1 in the database of ADP-ribosylated proteins, ADPriboDB (Vivelo et al, 2017). D Venn diagram of the proteins enriched by at least sixfold following HALO-NEDP1 CA pulldown compared with proteins identified as PARP-1 substrates in the database of ADP-ribosylated proteins, ADPriboDB (Vivelo et al, 2017).…”

Section: Mln4924mentioning

confidence: 99%

“…Blue markers indicate known components of the NEDD8 pathway, and red markers indicate proteins that have been identified as substrates of PARP-1 in the database of ADP-ribosylated proteins, ADPriboDB (Vivelo et al, 2017). D Venn diagram of the proteins enriched by at least sixfold following HALO-NEDP1 CA pulldown compared with proteins identified as PARP-1 substrates in the database of ADP-ribosylated proteins, ADPriboDB (Vivelo et al, 2017).…”

Section: Mln4924mentioning

confidence: 99%

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Unanchored tri‐NEDD8 inhibits PARP‐1 to protect from oxidative stress‐induced cell death

et al. 2019

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NEDD8 is a ubiquitin‐like protein that activates cullin‐RING E3 ubiquitin ligases (CRLs). Here, we identify a novel role for NEDD8 in regulating the activity of poly(ADP‐ribose) polymerase 1 (PARP‐1) in response to oxidative stress. We show that treatment of cells with H2O2 results in the accumulation of NEDD8 chains, likely by directly inhibiting the deneddylase NEDP1. One chain type, an unanchored NEDD8 trimer, specifically bound to the second zinc finger domain of PARP‐1 and attenuated its activation. In cells in which Nedp1 is deleted, large amounts of tri‐NEDD8 constitutively form, resulting in inhibition of PARP‐1 and protection from PARP‐1‐dependent cell death. Surprisingly, these NEDD8 trimers are additionally acetylated, as shown by mass spectrometry analysis, and their binding to PARP‐1 is reduced by the overexpression of histone de‐acetylases, which rescues PARP‐1 activation. Our data suggest that trimeric, acetylated NEDD8 attenuates PARP‐1 activation after oxidative stress, likely to delay the initiation of PARP‐1‐dependent cell death.

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Section: Mln4924mentioning

confidence: 99%

Section: Mln4924mentioning

confidence: 99%

Unanchored tri‐NEDD8 inhibits PARP‐1 to protect from oxidative stress‐induced cell death

et al. 2019

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“…One new hurdle is the identification of PARP substrate proteins, which would provide insight into the signaling pathways that are activated in response to pathogens. Several experimental protocols have been developed (48, 96, 224-226) and more than 2,000 ADP-ribosylation substrate proteins identified to date, and this area is in rapid development (113)(114)(115)(116)(117). Recently, new insight has been gained into the nature of PARylation consensus sequences and motifs, which to date has been elusive (96,227).…”

Section: Remaining Questionsmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

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SUMMARYThe literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.

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“…Informatics analyses revealed that RNA granule proteins are enriched for low complexity regions and these proteins are preferentially modified by ADP-ribosylation and that PAR-binding proteins are also enriched for low-complexity regions [27,[70][71][72]. Compared with other protein modifications that regulate SG dynamics, ADP-ribosylation is unique in that the polymeric form (i.e., PAR) is able to seed the low-complexity region-containing proteins to form non-membranous structures in vitro [25][26][27][28]70].…”

Section: Discussionmentioning

confidence: 99%

Alphavirus nsP3 ADP-ribosylhydrolase Activity Disrupts Stress Granule Formation

Jayabalan

Griffin

Leung

2019

Preprint

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Formation of stress granules (SGs), cytoplasmic condensates of stalled translation initiation complexes, is regulated by post-translational protein modification. Alphaviruses interfere with SG formation in response to inhibition of host protein synthesis through the activities of nonstructural protein 3 (nsP3). nsP3 has a conserved N-terminal macrodomain that binds and can remove ADP-ribose from ADPribosylated proteins and a C-terminal hypervariable domain that binds essential SG component G3BP1.We showed that the hydrolase activity of chikungunya virus nsP3 macrodomain removed ADPribosylation of G3BP1 and suppressed SG formation. ADP-ribosylhydrolase-deficient nsP3 mutants allowed stress-induced cytoplasmic condensation of translation initiation factors. nsP3 also disassembled SG-like aggregates enriched with translation initiation factors that are induced by the expression of FUS mutant R495X linked to amyotrophic lateral sclerosis. Therefore, our data indicate that regulation of ADP-ribosylation controls the localization of translation initiation factors during virus infection and other pathological conditions. All rights reserved. No reuse allowed without permission. INTRODUCTIONNon-membranous structures are prevalent in cells and critical for cellular functions, including RNA metabolism, embryonic cell fate specification, and neuronal activities [1][2][3]. Although the components of these non-membranous structures are often dynamically exchanged with the surrounding milieu, the compositions of these cellular structures remain distinct [4]. It is, however, unclear how individual components are selectively retained in these non-membranous structures.Stress granules (SGs), one of the best characterized dynamic non-membranous structures, are RNAprotein assemblies formed in response to a variety of environmental cues [3]. In most cases, these environmental cues activate stress-responsive protein kinases that phosphorylate the eukaryotic initiation factor 2 alpha (eIF2α), resulting in the stalling of translation initiation [3]. The sudden influx of untranslated mRNAs is proposed to seed the formation of SGs, where the polynucleotide promotes local concentration of proteins through non-covalent binding [5]. These RNA-binding proteins are highly enriched with low-complexity regions, and emergent data indicate that the nonspecific, weak interactions between these regions are responsible for the condensation of proteins to form higherorder structures, such as microscopically visible SGs [6][7][8]. Depending on the type of stress, the composition of SGs could vary [9], but certain common components, such as Ras GTP-activating protein-binding proteins G3BP1/2, are essential for SG formation [10,11]. Dysregulation of SG assembly/disassembly and mutations in the low-complexity region of specific SG proteins are implicated in the pathogenesis of diseases such as viral infection, cancer and neurodegeneration [1,[12][13][14]. Therefore, understanding the regulatory mechanisms of SG assembly is critical for designing novel th...

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ADPriboDB: The database of ADP-ribosylated proteins

Cited by 58 publications

References 52 publications

Unanchored tri‐NEDD8 inhibits PARP‐1 to protect from oxidative stress‐induced cell death

Unanchored tri‐NEDD8 inhibits PARP‐1 to protect from oxidative stress‐induced cell death

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Alphavirus nsP3 ADP-ribosylhydrolase Activity Disrupts Stress Granule Formation

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