Abstract
The ubiquitin proteasome system (UPS) plays a fundamental role in maintaining the correct balance of protein levels inside all living cells. Degradation of proteins by this pathway is essential for most cellular processes including cell signalling, DNA repair, apoptosis and gene transcription. Any disruption to the system is likely to have severe consequences which may lead to disorders including neurodegeneration and cancer. Ubiquitin protein ligases are a group of UPS proteins of particular importance because these proteins determine targeting specificity via recognition of a ‘target’ protein and its subsequent ‘tagging’ with ubiquitin. The 26S proteasome recognises these mutli-ubiquitylated proteins, allowing the correct protein to be degraded at the correct time and place within each cell. Several types of ubiquitin protein ligase have now been identified, however, the largest group by far are those proteins containing a ‘RING’ motif. In this review, examples will be given whereby abnormal protein ubiquitylation due to absence or inefficiency of a RING protein ligase is proposed to be a key regulator of the disease process. Ways in which we may be able to reverse these effects or manipulate these proteins to restore function will be discussed.
Keywords: Ubiquitin protein ligase, disease, small molecule inhibitors
Current Pharmaceutical Design
Title: Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases
Volume: 15 Issue: 31
Author(s): Helen C. Ardley
Affiliation:
Keywords: Ubiquitin protein ligase, disease, small molecule inhibitors
Abstract: The ubiquitin proteasome system (UPS) plays a fundamental role in maintaining the correct balance of protein levels inside all living cells. Degradation of proteins by this pathway is essential for most cellular processes including cell signalling, DNA repair, apoptosis and gene transcription. Any disruption to the system is likely to have severe consequences which may lead to disorders including neurodegeneration and cancer. Ubiquitin protein ligases are a group of UPS proteins of particular importance because these proteins determine targeting specificity via recognition of a ‘target’ protein and its subsequent ‘tagging’ with ubiquitin. The 26S proteasome recognises these mutli-ubiquitylated proteins, allowing the correct protein to be degraded at the correct time and place within each cell. Several types of ubiquitin protein ligase have now been identified, however, the largest group by far are those proteins containing a ‘RING’ motif. In this review, examples will be given whereby abnormal protein ubiquitylation due to absence or inefficiency of a RING protein ligase is proposed to be a key regulator of the disease process. Ways in which we may be able to reverse these effects or manipulate these proteins to restore function will be discussed.
Export Options
About this article
Cite this article as:
Ardley C. Helen, Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases, Current Pharmaceutical Design 2009; 15 (31) . https://dx.doi.org/10.2174/138161209789271807
DOI https://dx.doi.org/10.2174/138161209789271807 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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 Future of Induced Pluripotent Stem Cells for Cardiac Therapy and Drug Development
Current Pharmaceutical Design Current Perspectives on Anti-Aging Interventions
Letters in Drug Design & Discovery Critical Illness in Obstetric Patients: Introduction and Epidemiology
Current Women`s Health Reviews Endocrine Orchestration of Cardiovascular, Gastrointestinal and Hypothalamic Control
Current Medicinal Chemistry Non Invasive Imaging of Myocardial Infarction with Computed Tomography and Magnetic Resonance
Current Vascular Pharmacology Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas
Recent Advances in DNA & Gene Sequences (Discontinued) Sympathetic Activation in Congestive Heart Failure: Evidence, Consequences and Therapeutic Implications
Current Vascular Pharmacology Auto-Antibodies As Possible Markers and Mediators of Ischemic, Dilated, and Rhythmic Cardiopathies
Current Drug Targets Omega-3 Fatty Acids: Role in Metabolism and Cardiovascular Disease
Current Pharmaceutical Design The Two Faces of Iminoalditols: Powerful Inhibitors Trigger Glycosidase Activation
Current Enzyme Inhibition How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization
Mini-Reviews in Medicinal Chemistry Cannabinoid Receptor Type 2 Activation in Atherosclerosis and Acute Cardiovascular Diseases
Current Medicinal Chemistry Clinical Approach to Diabetic Cardiomyopathy: A Review of Human Studies
Current Medicinal Chemistry Meet Our Editorial Board Member:
Current Diabetes Reviews A Review of Therapeutic Effects of Curcumin
Current Pharmaceutical Design Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis
Current Cardiology Reviews Pentraxins: CRP and PTX3 and Cardiovascular Disease
Inflammation & Allergy - Drug Targets (Discontinued) Kinin Receptors in Vascular Biology and Pathology
Current Vascular Pharmacology Current Use of Cardiac Biomarkers in Various Heart Conditions
Endocrine, Metabolic & Immune Disorders - Drug Targets Using Extracellular Matrix-Derived Peptides to Alter the Microenvironment for Myocardial Repair
Current Vascular Pharmacology