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
-
Anticancer Perspectives on the Fungal-Derived Polyphenolic Hispolon
Anti-Cancer Agents in Medicinal Chemistry New Targets, New Agents, and the Evolving Phenomena of Drug Resistance in Cancer
Current Cancer Therapy Reviews New Antimicrobial Frontiers
Mini-Reviews in Medicinal Chemistry Human Sirtuins: An Overview of an Emerging Drug Target in Age-Related Diseases and Cancer
Current Drug Targets B Cell Modulation Strategies in Autoimmunity: The SLE Example
Current Pharmaceutical Design The Development of Copper Radiopharmaceuticals for Imaging and Therapy
Medicinal Chemistry The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib
Current Pharmaceutical Design Metallic Colloid Nanotechnology, Applications in Diagnosis and Therapeutics
Current Pharmaceutical Design In Vitro Antitumoral Activity of Palladium(II) and Platinum(II) Complexes with O,O'-Dialkyl Esters of Ethylene-bis(S)-Leucine
Letters in Drug Design & Discovery Meet Our Editorial Board Member
Current Medicinal Chemistry Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology The Endothelin Axis as Therapeutic Target in Human Malignancies: Present and Future
Current Pharmaceutical Design The Emerging Pharmacology of TRPM8 Channels: Hidden Therapeutic Potential Underneath a Cold Surface
Current Pharmaceutical Biotechnology Focus on the Role of Glutamate in the Pathology of the Peripheral Nervous System
CNS & Neurological Disorders - Drug Targets Cytosine Methyltransferases as Tumor Markers
Current Genomics Dysregulated Post-Transcriptional Control of COX-2 Gene Expression in Cancer
Current Pharmaceutical Design Chemokine Like Receptor-1 (CMKLR-1) Receptor: A Potential Therapeutic Target in Management of Chemerin Induced Type 2 Diabetes Mellitus and Cancer
Current Pharmaceutical Design Malignant Mesothelioma Resistance to Apoptosis: Recent Discoveries and their Implication for Effective Therapeutic Strategies
Current Medicinal Chemistry Synergistic Approaches to Clinical Oncology Biomarker Discovery
Current Topics in Medicinal Chemistry Radiosynthesis of N.C.A. Sodium [18F]Fluoroacetate and Radiopharmacological Characterization in Rats and Tumor-Xenografted Mice
Current Radiopharmaceuticals