Abstract
The post-translational modifications of proteins by mono- and poly-ADP-ribosylation involve the cleavage of βNAD+, with the release of its nicotinamide moiety, accompanied by the transfer of a single (mono) or several (poly) ADP-ribose molecules from βNAD+ to a specific amino-acid residue of various cellular proteins. Thus, both mono- and poly-ADP-ribosylation are NAD+-consuming reactions. ADP-ribosylation reactions have been reported to have important roles in the nucleus, and in mitochondrial activity. Distinct subcellular NAD+ pools have been identified, not only in the nucleus and the mitochondria, but also in the endoplasmic reticulum and peroxisomes. Recent reports have shed new light on the correlation between NAD+-dependent ADP-ribosylation reactions and the endoplasmic reticulum. We have demonstrated that ARTD15/PARP16 is a novel mono-ADP-ribosyltransferase with a new intracellular location, as it is associated with the endoplasmic reticulum. The endoplasmic reticulum is a membranous network of tubules, vesicles, and cisternae that are interconnected in the cytoplasm of eukaryotic cells. This intracellular compartment is responsible for many cellular functions, including facilitation of protein folding and assembly, biosynthesis of lipids, storage of intracellular Ca2+, and transport of proteins. ARTD15 might have a role in both the nucleo-cytoplasmic shuttling, through importinβ1 mono-ADP-ribosylation, and in the unfolded protein response through its ability to ADP-ribosylate two components of this pathway: PERK and IRE1. This review summarizes our present knowledge of the enzymes and targets involved in ADP-ribosylation reactions, with special regard to the novel regulatory reactions that occurs at the level of the endoplasmic reticulum, and that can affect the function of this organelle.
Keywords: ADP-ribosyltransferase, ARTD, ARTC, endoplasmic reticulum, Importinβ1, NAD, Post-translational modification, UPR.
Current Topics in Medicinal Chemistry
Title:NAD+-Dependent Enzymes at the Endoplasmic Reticulum
Volume: 13 Issue: 23
Author(s): Maria Di Girolamo, Gaia Fabrizio, Emanuele Salvatore Scarpa and Simone Di Paola
Affiliation:
Keywords: ADP-ribosyltransferase, ARTD, ARTC, endoplasmic reticulum, Importinβ1, NAD, Post-translational modification, UPR.
Abstract: The post-translational modifications of proteins by mono- and poly-ADP-ribosylation involve the cleavage of βNAD+, with the release of its nicotinamide moiety, accompanied by the transfer of a single (mono) or several (poly) ADP-ribose molecules from βNAD+ to a specific amino-acid residue of various cellular proteins. Thus, both mono- and poly-ADP-ribosylation are NAD+-consuming reactions. ADP-ribosylation reactions have been reported to have important roles in the nucleus, and in mitochondrial activity. Distinct subcellular NAD+ pools have been identified, not only in the nucleus and the mitochondria, but also in the endoplasmic reticulum and peroxisomes. Recent reports have shed new light on the correlation between NAD+-dependent ADP-ribosylation reactions and the endoplasmic reticulum. We have demonstrated that ARTD15/PARP16 is a novel mono-ADP-ribosyltransferase with a new intracellular location, as it is associated with the endoplasmic reticulum. The endoplasmic reticulum is a membranous network of tubules, vesicles, and cisternae that are interconnected in the cytoplasm of eukaryotic cells. This intracellular compartment is responsible for many cellular functions, including facilitation of protein folding and assembly, biosynthesis of lipids, storage of intracellular Ca2+, and transport of proteins. ARTD15 might have a role in both the nucleo-cytoplasmic shuttling, through importinβ1 mono-ADP-ribosylation, and in the unfolded protein response through its ability to ADP-ribosylate two components of this pathway: PERK and IRE1. This review summarizes our present knowledge of the enzymes and targets involved in ADP-ribosylation reactions, with special regard to the novel regulatory reactions that occurs at the level of the endoplasmic reticulum, and that can affect the function of this organelle.
Export Options
About this article
Cite this article as:
Girolamo Di Maria, Fabrizio Gaia, Scarpa Salvatore Emanuele and Paola Di Simone, NAD+-Dependent Enzymes at the Endoplasmic Reticulum, Current Topics in Medicinal Chemistry 2013; 13 (23) . https://dx.doi.org/10.2174/15680266113136660214
DOI https://dx.doi.org/10.2174/15680266113136660214 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Reciprocal Interaction: Chemotherapy and Tumor Microenvironment
Current Drug Discovery Technologies Targeting the Expression of Anti-Apoptotic Proteins by Antisense Oligonucleotides
Current Drug Targets Exploring the Management of Statin Intolerant Patients: 2016 and Beyond
Current Vascular Pharmacology Dual Topoisomerase I / II Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment
Current Cancer Therapy Reviews Novel Therapeutic Approaches Targeting Vascular Endothelial Growth Factor and its Receptors in Haematological Malignancies
Current Cancer Drug Targets Divergent Synthesis of Novel Dienylbenzothiazoles and Arylidenedibenzoxazepines and Evaluation of Their Antiproliferative and Cytotoxic Properties
Letters in Organic Chemistry Simultaneous determination of Curcumin (Cur) and Thymoquinone (THQ) in lipid based self-nanoemulsifying systems and its application to the commercial product using UHPLC-UV-Vis spectrophotometer
Current Pharmaceutical Analysis Diabetes, Cancer and Treatment – A Mini-Review
Current Drug Safety Cross-Talk between Tumor Cells and the Microenvironment at the Metastatic Niche
Current Pharmaceutical Biotechnology Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Syntheses and Antitumor Activities of Potent Inhibitors of Ribonucleotide Reductase: 3-Amino-4-Methylpyridine-2-Carboxaldehyde-Thiosemicarbazone (3-Amp), 3-Amino-Pyridine-2-Carboxaldehyde-Thiosemicarbazone (3-Ap) and its Water-Soluble Prodrugs
Current Medicinal Chemistry Bioconjugation of Polymers: A Novel Platform for Targeted Drug Delivery
Current Pharmaceutical Design The Role of Oxidative Stress in Smoking-Related Diseases
Mini-Reviews in Organic Chemistry The use of nanocarriers in acute myeloid leukaemia therapy: challenges and current status.
Current Pharmaceutical Biotechnology Long Chain n-3 Polyunsaturated Fatty Acids in the Prevention of Allergic and Cardiovascular Disease
Current Pharmaceutical Design Tyrosine Kinase Inhibitors
Current Cancer Drug Targets Cinnamic Acid Derivatives as Anticancer Agents-A Review
Current Medicinal Chemistry Molecular Mechanism of Aniline Induced Spleen Toxicity and Neuron Toxicity in Experimental Rat Exposure: A Review
Current Neuropharmacology Synthesis and Biological Evaluation of 3,4-Dihydro-3-(3-methylisoxazol-5- yl)-2H-benzo[e][1,3]oxazine Derivatives as Anticancer Agents
Letters in Organic Chemistry