Special Issue "Poly ADP ribose polymerases (PARP) and post-translational modifications"

A special issue of Challenges (ISSN 2078-1547).

Deadline for manuscript submissions: closed (15 April 2018)

Special Issue Editors

Guest Editor
Dr. Palmiro Poltronieri

National Research Council of Italy, AgroFood Department, Institute of Sciences of Food Productions, Lecce, Italy
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Interests: biotechnologies for the quality and safety of food productions; microbiology and quality of food productions
Guest Editor
Dr. Mariella Di Girolamo

Laboratory of Signal Transduction “Mario Negri Sud” Center for Pharmacological and Biomedical Research, S. Maria Imbaro (Chieti), Italy
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Guest Editor
Prof. Dr. Masanao Miwa

Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan
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Special Issue Information

Dear Colleagues,

In Budapest, the PARP 2017 meeting (14–16 May, 2017) will be hosted at the National Academy of Science. The website for the meeting is http://ki.se/en/mbb/parp2017. Challenges is promoting the congress with the best poster award. Recently may advances have been made, such as PARylation in serine, with the identification of PARP coactivators promoting this activity, such as histone PARylation factor 1 (HPF1). In plants, the first PARP substrate has been identified, Dawdle (DDL), a Forkhead-associated (FHA) domain protein with multiple PARylation sites, which positively regulates plant immunity. Among prokariotic ADP ribosyl hydrolases, the Chikungunya virus macro-domain has been characterized. The macro-domain has multiple roles, such as in stress granule formation, which counteracts PARP-16 Marylation, either by hydrolyzing activity, either by binding to polymer domains: this prevents the access to the ADP-ribose moiety to other interaction partners. Finally, PARP activities have an excellent potential for pharmacological interventions: the field of new inhibitors of PArylation has great expectations in cancer treatment for BRCA1-mutated patients. We expect that the PAR/MAR regulation will bring novel developments and applications to scientific fields, such as bacterial toxins, viruses, plant immunity and various aspects of chromatin structure, transcription regulation, and epigenetic control in animal and plant cells.

Dr. Palmiro Poltronieri
Dr. Mariella Di Girolamo
Prof. Dr. Masanao Miwa
Guest Editors

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Keywords

  • poly ADP-ribosylation (Parylation)
  • mono ADP ribosylation (Marylation)
  • amino acid modification
  • coactivator proteins
  • glycohydrolases
  • inhibitors
  • gene knock outs
  • animals
  • plants
  • bacteria
  • protein-protein interactions
  • Transcription Factors
  • Gene expression

Published Papers (6 papers)

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Research

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Open AccessArticle Measurement of Poly(ADP-ribose) Level with Enhanced Slot Blot Assay with Crosslinking
Challenges 2018, 9(2), 27; https://doi.org/10.3390/challe9020027
Received: 29 March 2018 / Revised: 22 June 2018 / Accepted: 26 June 2018 / Published: 2 July 2018
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Abstract
Poly(ADP-ribose) (PAR) formation is catalyzed by poly(ADP-ribose) polymerase (PARP) family proteins in nuclei as well as in cytosols. The anti-PAR antibodies that specifically detect PAR are useful for the quantitative measurement of PAR in cells, in tissue, and in the body. In clinical
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Poly(ADP-ribose) (PAR) formation is catalyzed by poly(ADP-ribose) polymerase (PARP) family proteins in nuclei as well as in cytosols. The anti-PAR antibodies that specifically detect PAR are useful for the quantitative measurement of PAR in cells, in tissue, and in the body. In clinical trials of PARP inhibitors, a pharmacodynamic (PD) assay for the measurement of PARP activity inhibition in peripheral blood mononuclear cells (PBMCs) with dot-blot assay or an ELISA assay using anti-PAR antibodies have been used. In these assays, ex vivo PARP activity and its inhibition assay have been used. For a PD assay to assess the efficacy of the treatment, the measurement of PARP activity inhibition in tumor tissues/cells has been recommended. A dot or slot blot assay may also be suitable for the measurement of such crude tissue samples. Here, we investigate the optimum conditions for a dot/slot blot assay of an ex vivo PARP activity assay by utilizing physical and chemical crosslinking methods. Using 10H monoclonal antibody to PAR, we show that use of a nylon membrane and UV crosslink at 254 nm can stably enhance the detection level of PAR. However, the limitation of this assay is that the size of PAR detectable using the 10H antibody must be around 20 ADP-ribose residues, since the antibody cannot bind PAR of lower size. Full article
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Open AccessArticle ARTD10/PARP10 Induces ADP-Ribosylation of GAPDH and Recruits GAPDH into Cytosolic Membrane-Free Cell Bodies When Overexpressed in Mammalian Cells
Challenges 2018, 9(1), 22; https://doi.org/10.3390/challe9010022
Received: 22 February 2018 / Revised: 27 April 2018 / Accepted: 27 April 2018 / Published: 3 May 2018
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Abstract
Protein ADP-ribosylation is a reversible post-translational modification of cellular proteins that is catalysed by enzymes that transfer one (mono) or several (poly) units of ADP-ribose from β-NAD+ to a specific amino acid of the target protein. The most studied member of the
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Protein ADP-ribosylation is a reversible post-translational modification of cellular proteins that is catalysed by enzymes that transfer one (mono) or several (poly) units of ADP-ribose from β-NAD+ to a specific amino acid of the target protein. The most studied member of the ADP-ribosyltransferase family is PARP1 (also known as ADP-ribosyltransferase diphtheria toxin-like 1, ARTD1), which is directly activated by DNA strand breaks and is involved in DNA damage repair, chromatin remodelling and transcriptional regulation. Much less is known about the further 16 members of this family. Among these, ARTD10/PARP10 has been previously characterised as a mono-ADP-ribosyltransferase with a role in cell proliferation and in NF-kB signalling. In the present study, we identified the glycolytic enzyme GAPDH as an interactor and a novel cellular target for ARTD10/PARP10. Moreover, we detected the co-localisation of GAPDH and ARTD10/PARP10 in well-defined cytosolic bodies, which we show here to be membrane-free, rounded structures using immunogold labelling and electron microscopy. Using the cognitive binding module macro domain to visualise ADP-ribosylated proteins by immunofluorescence microscopy in cells over-expressing the ARTD10/PARP10 enzyme, we show that the staining of the ARTD10/PARP10-dependent cytosolic bodies was lost when the cells were treated with compounds that inhibit ARTD10/PARP10, either by directly inhibiting the enzyme or by reducing the cellular NAD+ levels. In parallel, the same treatment affected the co-localisation of GAPDH and ARTD10/PARP10, as GAPDH disappeared from the cytosolic cell bodies, which indicates that its presence there depends on the catalytic activity of ARTD10/PARP10. In line with this, in cells over-expressing the ARTD10/PARP10 catalytic domain alone, which we show here to form stress granules, GAPDH was recruited into stress granules. These data identify ARTD10/PARP10 as the enzyme that modifies and recruits GAPDH into cytosolic structures. Full article
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Review

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Open AccessReview The ADP-Ribosyl-Transferases Diphtheria Toxin-Like (ARTDs) Family: An Overview
Challenges 2018, 9(1), 24; https://doi.org/10.3390/challe9010024
Received: 11 April 2018 / Revised: 22 May 2018 / Accepted: 24 May 2018 / Published: 27 May 2018
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Abstract
Poly-ADP-ribosylation is a post-translational modification that occurs in multicellular organisms, including plants and some lower unicellular eukaryotes. The founding member of the PARP family is PARP1. To date, 17 members of the PARP family have been identified, which differ from each other in
[...] Read more.
Poly-ADP-ribosylation is a post-translational modification that occurs in multicellular organisms, including plants and some lower unicellular eukaryotes. The founding member of the PARP family is PARP1. To date, 17 members of the PARP family have been identified, which differ from each other in terms of domain organization, transmodification targets, cellular localization, and biological functions. In recent years, considering structural and biochemical features of the different members of the PARP family, a new classification has been proposed. Thus, enzymes firstly classified as PARP are now named diphtheria-toxin-like ARTs, abbreviated to ARTDs, in accordance with the prototype bacterial toxin that their structural aspects resemble, with numbers indicating the different proteins of the family. The 17 human ARTD enzymes can be divided on the basis of their catalytic activity into polymerases (ARTD1–6), mono-ADP-ribosyl-transferases (ARTD7–17), and the inactive ARTD13. In recent years, ADP-ribosylation was intensively studied, and research was dominated by studies focusing on the role of this modification and its implication on various cellular processes. The aim of this review is to provide a general overview of the ARTD enzymes, with a special focus on mono-ARTDs. Full article
Open AccessReview In Vivo Level of Poly(ADP-ribose)
Challenges 2018, 9(1), 23; https://doi.org/10.3390/challe9010023
Received: 10 April 2018 / Revised: 18 May 2018 / Accepted: 18 May 2018 / Published: 22 May 2018
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Abstract
PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of
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PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of polyADP-ribosylation, it is necessary to quantify and monitor the change of the in vivo level of PAR, the product of polyADP-ribosylation, which is rapidly turning over and kept in quite low level in cells or in organs. Recent developments of potent inhibitors of polyADP-ribosylation is expected to kill BRCA1/2-mutated breast cancer cells and ovarian cancer cells (synthetic lethality). To know the efficacy of these inhibitors in vivo, it is necessary to develop highly sensitive and reproducible methods to know PAR levels within cells or organs. However there have been several difficulties in measuring the physiologically low level of PAR without artefacts. Our experiments recently clarified that the method of sample preparation is very important in addition to the sensitivity and specificity. From reviewing the literature, including ours, we would like to emphasize the importance of the procedures of sample preparation for the assay, in addition to the sensitivity by comparing the reported PAR levels in vivo. Full article
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Open AccessReview The Dichotomy of the Poly(ADP-Ribose) Polymerase-Like Thermozyme from Sulfolobus solfataricus
Challenges 2018, 9(1), 5; https://doi.org/10.3390/challe9010005
Received: 13 December 2017 / Revised: 28 January 2018 / Accepted: 30 January 2018 / Published: 31 January 2018
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Abstract
The first evidence of an ADP-ribosylating activity in Archaea was obtained in Sulfolobus solfataricus(strain MT-4) where a poly(ADP-ribose) polymerase (PARP)-like thermoprotein, defined with the acronymous PARPSso, was found. Similarly to the eukaryotic counterparts PARPSso cleaves beta-nicotinamide adenine dinucleotide to synthesize oligomers of
[...] Read more.
The first evidence of an ADP-ribosylating activity in Archaea was obtained in Sulfolobus solfataricus(strain MT-4) where a poly(ADP-ribose) polymerase (PARP)-like thermoprotein, defined with the acronymous PARPSso, was found. Similarly to the eukaryotic counterparts PARPSso cleaves beta-nicotinamide adenine dinucleotide to synthesize oligomers of ADP-ribose; cross-reacts with polyclonal anti-PARP-1 catalytic site antibodies; binds DNA. The main differences rely on the molecular mass (46.5 kDa) and the thermophily of PARPSso which works at 80 °C. Despite the biochemical properties that allow correlating it to PARP enzymes, the N-terminal and partial amino acid sequences available suggest that PARPSso belongs to a different group of enzymes, the DING proteins, an item discussed in detail in this review.This finding makes PARPSso the first example of a DING protein in Archaea and extends the existence of DING proteins into all the biological kingdoms. PARPSsohas a cell peripheral localization, along with the edge of the cell membrane. The ADP-ribosylation reaction is reverted by a poly(ADP-ribose) glycohydrolase-like activity, able to use the eukaryotic poly(ADP-ribose) as a substrate too. Here we overview the research of (ADP-ribosyl)ation in Sulfolobus solfataricus in the past thirty years and discuss the features of PARPSso common with the canonical poly(ADP-ribose) polymerases, and the structure fitting with that of DING proteins. Full article
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Open AccessReview Roles of Nicotinamide Adenine Dinucleotide (NAD+) in Biological Systems
Challenges 2018, 9(1), 3; https://doi.org/10.3390/challe9010003
Received: 12 December 2017 / Revised: 12 January 2018 / Accepted: 16 January 2018 / Published: 19 January 2018
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Abstract
NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation
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NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl groups from proteins; NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in Ca++ release and signaling, and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2′-5′A), two immune response activating compounds. In the biological systems considered in this review, NAD+ is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, two types of ADP-ribosylating enzymes are introduced as well as the pathways to restore the NAD+ pools in these systems. Full article
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