PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Welsby, Iain; Hutin, David; Gueydan, Cyril; Kruys, Véronique; Rongvaux, Anthony; Léo, Oberdan

doi:10.1074/jbc.m114.589515

Cited by 98 publications

(121 citation statements)

References 62 publications

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“…Very little is understood about the function of these primarily cytoplasmic PARPs. PARP7 (also referred to as TCDD inducible PARP, TiPARP) and PARP12 play a role in immune responses mediating T cell activation and inflammation (Welsby et al, 2014), and PARP13 has been described as an anti-retroviral protein (Gao et al, 2002). All CCCH PARPs contain uncharacterized WWE domains (Figure 2).…”

Section: The Macro Parpsmentioning

confidence: 99%

Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation

2015

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The poly(ADP-ribose) polymerases (PARPs) are a major family of enzymes capable of modifying proteins by ADP-ribosylation. Due to the large size and diversity of this family, PARPs affect almost every aspect of cellular life and have fundamental roles in DNA repair, transcription, heat shock and cytoplasmic stress responses, cell division, protein degradation, and much more. In the past decade, our understanding of the PARP enzymatic mechanism and activation, as well as regulation of ADP-ribosylation signals by the readers and erasers of protein ADP-ribosylation, has been significantly advanced by the emergence of new structural data, reviewed herein, which allow for better understanding of the biological roles of this widespread post-translational modification.

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Section: The Macro Parpsmentioning

confidence: 99%

Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation

2015

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“…In this regard, intracellular PARP-12 expression is up-regulated upon stimulation by type II interferons (Welsby et al 2014). Furthermore, ectopic expression of PARP-12 leads to increased NF-κB signaling, implicating PARP-12 in cellular immune responses (Welsby et al 2014).…”

Section: Role Of Parp Monoenzymes and Catalytically Inactive Parps Inmentioning

confidence: 99%

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

2017

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The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.ADP-ribosylation is a reversible post-translational modification (PTM) of proteins resulting in the covalent attachment of a single ADP-ribose unit [i.e., mono(ADP-ribose) (MAR)] or polymers of ADP-ribose units [i.e., poly(ADP-ribose) (PAR)] on a variety of amino acid residues on target proteins (Gibson and Kraus 2012;Daniels et al. 2015a). This modification is mediated by a diverse group of ADPribosyl transferase (ADPRT) enzymes that use ADP-ribose units derived from β-NAD + to catalyze the ADP-ribosylation reaction. These enzymes include bacterial ADPRTs (e.g., cholera toxin and diphtheria toxin) as well as members of three different protein families in yeast and animals: (1) arginine-specific ecto-enzymes (ARTCs), (2) sirtuins, and (3) PAR polymerases (PARPs) . Surprisingly, a recent study showed that the bacterial toxin DarTG can ADP-ribosylate DNA . How this fits into the broader picture of cellular ADP-ribosylation has yet to be determined.In this review, we focus on the mono(ADP-ribosyl)ation (MARylation) and poly(ADP-ribosyl)ation (PARylation) of glutamate, aspartate, and lysine residues by PARP family members. While many reviews have been written on PARPs in the past decade, we highlight the current trends and ideas in the field, in particular those discoveries that have been published in the past 2-3 years.

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“…[35] It was also reported that PARP12 has a functional role in stress response. [36] Additionally expression of damage-specific DNA binding protein 2 (DDB2) was upregulated twofold. mRNA levels of a major non-homologous end joining (NHEJ) pathway protein, XRCC4, were downregulated 0.5-fold, which aligned with our proteomics analysis that showed BRCA1-mediated responses, which are part of a homologous recombination pathway.…”

Section: Resultsmentioning

confidence: 99%

A ROS‐Activatable Agent Elicits Homologous Recombination DNA Repair and Synergizes with Pathway Compounds

et al. 2015

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We designed ROS-activated cytotoxic agents (RACs) that are active against AML cancer cells. In this study, the mechanism of action and synergistic effects against cells coexpressing the AML oncogenes MLL-AF9 fusion and FLT3-ITD were investigated. One RAC (RAC1) had an IC50 value of 1.8 ± 0.3 µm, with ninefold greater selectivity for transformed cells compared to untransformed cells. Treatment induced DNA strand breaks, apoptosis, and cell cycle arrest. Proteomics and transcriptomics revealed enhanced expression of the pentose phosphate pathway, DNA repair, and pathways common to cell stress. Western blotting confirmed repair by homologous recombination. Importantly, RAC1 treatment was synergistic in combination with multiple pathway-targeting therapies in AML cells but less so in untransformed cells. Together, these results demonstrate that RAC1 can selectively target poor prognosis AML and that it does so by creating DNA double-strand breaks that require homologous recombination.

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PARP12, an Interferon-stimulated Gene Involved in the Control of Protein Translation and Inflammation

Cited by 98 publications

References 62 publications

Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation

Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

A ROS‐Activatable Agent Elicits Homologous Recombination DNA Repair and Synergizes with Pathway Compounds

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