Abstract
Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in various cellular functions, such as telomere homeostasis, Wnt/β-catenin signaling, glucose metabolism, and cell cycle progression. In these processes, Tankyrases regulate the interactions and stability of target proteins by poly (ADP-ribosyl)ation. Modified proteins are subsequently recognized by the E3 ubiquitin ligase RNF146, poly-ubiquitinated and predominantly guided to 26S proteasomal degradation. Several small molecule inhibitors have been described for Tankyrases; they compete with the co-substrate NAD+ for binding to the ARTD catalytic domain. The recent, highly potent and selective inhibitors possess several properties of lead compounds and can be used for proof-of-concept studies in cancer and other Tankyrase linked diseases.
Keywords: Cancer, drug design, enzyme, inhibitor, tankyrase, telomere, Wnt/β-catenin signaling.
Current Pharmaceutical Design
Title:Tankyrases: Structure, Function and Therapeutic Implications in Cancer
Volume: 20 Issue: 41
Author(s): Teemu Haikarainen, Stefan Krauss and Lari Lehtio
Affiliation:
Keywords: Cancer, drug design, enzyme, inhibitor, tankyrase, telomere, Wnt/β-catenin signaling.
Abstract: Several cellular signaling pathways are regulated by ADP-ribosylation, a posttranslational modification catalyzed by members of the ARTD superfamily. Tankyrases are distinguishable from the rest of this family by their unique domain organization, notably the sterile alpha motif responsible for oligomerization and ankyrin repeats mediating protein-protein interactions. Tankyrases are involved in various cellular functions, such as telomere homeostasis, Wnt/β-catenin signaling, glucose metabolism, and cell cycle progression. In these processes, Tankyrases regulate the interactions and stability of target proteins by poly (ADP-ribosyl)ation. Modified proteins are subsequently recognized by the E3 ubiquitin ligase RNF146, poly-ubiquitinated and predominantly guided to 26S proteasomal degradation. Several small molecule inhibitors have been described for Tankyrases; they compete with the co-substrate NAD+ for binding to the ARTD catalytic domain. The recent, highly potent and selective inhibitors possess several properties of lead compounds and can be used for proof-of-concept studies in cancer and other Tankyrase linked diseases.
Export Options
About this article
Cite this article as:
Haikarainen Teemu, Krauss Stefan and Lehtio Lari, Tankyrases: Structure, Function and Therapeutic Implications in Cancer, Current Pharmaceutical Design 2014; 20 (41) . https://dx.doi.org/10.2174/1381612820666140630101525
DOI https://dx.doi.org/10.2174/1381612820666140630101525 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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 Role of PET/CT and SPECT/CT in Oncology Drug Development
Current Molecular Imaging (Discontinued) RNA Silencing: Recent Developments on miRNAs
Recent Patents on DNA & Gene Sequences The Roles of Chromatin Remodeling Proteins in Cancer
Current Protein & Peptide Science Pattern Recognition by CD6: A Scavenger-Like Lymphocyte Receptor
Current Drug Targets Engineered Polymer Nanoplatforms for Targeted Tumor Cells and Controlled Release Cargos to Enhance Cancer Treatment
Current Medicinal Chemistry Pharmacological Inhibition of the Bcl-2 Family of Apoptosis Regulators as Cancer Therapy
Current Molecular Pharmacology Molecular Insight and Binding Pattern Analysis of Shikonin as a Potential VEGFR-2 Inhibitor
Current Enzyme Inhibition Strategies for the Assessment of Metabolic Profiles of Steroid Hormones in View of Diagnostics and Drug Monitoring: Analytical Problems and Challenges
Current Drug Metabolism Are Selenoproteins Important for the Cancer Protective Effects of Selenium?
Current Nutrition & Food Science Discovery of Anticancer Agents from 2-Pyrazoline-Based Compounds
Current Medicinal Chemistry Targeting p73 - a Potential Approach in Cancer Treatment
Current Pharmaceutical Design Phenolics and Terpenoids; the Promising New Search for Anthelmintics: A Critical Review
Mini-Reviews in Medicinal Chemistry Lyn Regulates Cytotoxicity in Respiratory Epithelial Cells Challenged by Cigarette Smoke Extracts
Current Molecular Medicine Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?
Current Drug Metabolism Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?
Central Nervous System Agents in Medicinal Chemistry A Hybrid Discrete Imperialist Competition Algorithm for Gene Selection for Microarray Data
Current Proteomics The Radionuclide Molecular Imaging and Therapy of Neuroendocrine Tumors
Current Cancer Drug Targets Gene Therapy in In Vivo Isolated Perfusion Models
Current Gene Therapy Heteroaromatic Pim Kinase Inhibitors Containing a Pyrazole Moiety
Recent Patents on Anti-Cancer Drug Discovery Antigene and Antiproliferative Effects of Triplex-Forming Oligonucleotide (TFO) Targeted on hmgb1 Gene in Human Hepatoma Cells
Anti-Cancer Agents in Medicinal Chemistry