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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...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
-
An Overview of the α4β1 Integrin and the Potential Therapeutic Role of its Antagonists
Current Medicinal Chemistry Metastatic Breast Cancer, Organotropism and Therapeutics: A Review
Current Cancer Drug Targets Immunotherapy in Non-Small Cell Lung Cancer: Biological Principles and Future Opportunities
Current Molecular Medicine The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications
Current Genomics A Potential Anticancer Agent 1,2-di(quinazolin-4-yl)diselane
Letters in Drug Design & Discovery Health Beneficial Potential of Pectolinarigenin on Human Diseases: An Updated Review of Medicinal Importance and Pharmacological Activity
The Natural Products Journal Preclinical and Clinical Studies of Chidamide (CS055/HBI-8000), An Orally Available Subtype-selective HDAC Inhibitor for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Resveratrol Counteracts Hypoxia-Induced Gastric Cancer Invasion and EMT through Hedgehog Pathway Suppression
Anti-Cancer Agents in Medicinal Chemistry Radiolabeled Small Molecule Inhibitors of VEGFR - Recent Advances
Current Pharmaceutical Design Current Trends in the Use of Cationic Polymer Assemblies for siRNA and Plasmid DNA Delivery
Pharmaceutical Nanotechnology Vitamin D: A Pleiotropic Hormone with Possible Psychotropic Activities
Current Medicinal Chemistry Antiangiogenic Therapy and Ovarian Cancer
Current Women`s Health Reviews Pharmacological Approaches for BRCA1/2 Related Breast and Ovarian Cancer: Preclinical Studies and Early Clinical Trials
Current Women`s Health Reviews Clinical Application of Percutaneous Puncture Biopsy Guided by Fused and 3D-reconstructed PET/CT Images
Current Medical Imaging α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Regulation of ABCB1 Transporter Expression and Function
Current Pharmacogenomics and Personalized Medicine Overcoming Drug Resistance by Enhancing Apoptosis of Tumor Cells
Current Cancer Drug Targets Dibenzoylmethane Activates Nrf2-Dependent Detoxification Pathway and Inhibits Benzo(a)pyrene Induced DNA Adducts in Lungs
Medicinal Chemistry Progress Toward Vector Design for Hematopoietic Stem Cell Gene Therapy
Current Gene Therapy Rheumatoid Nodules and Lung
Current Respiratory Medicine Reviews