Abstract
Members of the Really Interesting New Gene (RING) family of proteins are found throughout the cells of eukaryotes and function in processes as diverse as development, oncogenesis, viral replication and apoptosis. There are over 200 members of the RING family where membership is based on the presence of a consensus sequence of zinc binding residues. Outside of these residues there is little sequence homology; however, there are conserved structural features. Current evidence strongly suggests that RINGs are protein interaction domains. We examine the features of RING binding motifs in terms of individual cases and the potential for finding a universal consensus sequence for RING binding domains (FRODOs). This review examines known and potential functions of RINGs, and attempts to develop a framework within which their seemingly multivalent cellular roles can be consistently understood in their structural and biochemical context. Interestingly, some RINGs can selfassociate as well as bind other RINGs. The ability to self-associate is typically translated into the annoying propensity of these domains to aggregate during biochemical characterization. The RINGs of PML, BRCA1, RAG1, KAP1/TIF1β, Polycomb proteins, TRAFs and the viral protein Z have been well characterized in terms of both biochemical studies and functional data and so will serve as focal points for discussion. We suggest physiological functions for the oligomeric properties of these domains, such as their role in formation of macromolecular assemblages which function in an intricate interplay of coupled metal binding, folding and aggregation, and participate in diverse functions: epigenetic regulation of gene expression, RNA transport, cell cycle control, ubiquitination, signal transduction and organelle assembly.
Current Protein & Peptide Science
Title: Construction of Macromolecular Assemblages in Eukaryotic Processes and their Role in Human Disease: Linking RINGs Together
Volume: 1 Issue: 1
Author(s): A. Kentsis and K. L. B. Borden
Affiliation:
Abstract: Members of the Really Interesting New Gene (RING) family of proteins are found throughout the cells of eukaryotes and function in processes as diverse as development, oncogenesis, viral replication and apoptosis. There are over 200 members of the RING family where membership is based on the presence of a consensus sequence of zinc binding residues. Outside of these residues there is little sequence homology; however, there are conserved structural features. Current evidence strongly suggests that RINGs are protein interaction domains. We examine the features of RING binding motifs in terms of individual cases and the potential for finding a universal consensus sequence for RING binding domains (FRODOs). This review examines known and potential functions of RINGs, and attempts to develop a framework within which their seemingly multivalent cellular roles can be consistently understood in their structural and biochemical context. Interestingly, some RINGs can selfassociate as well as bind other RINGs. The ability to self-associate is typically translated into the annoying propensity of these domains to aggregate during biochemical characterization. The RINGs of PML, BRCA1, RAG1, KAP1/TIF1β, Polycomb proteins, TRAFs and the viral protein Z have been well characterized in terms of both biochemical studies and functional data and so will serve as focal points for discussion. We suggest physiological functions for the oligomeric properties of these domains, such as their role in formation of macromolecular assemblages which function in an intricate interplay of coupled metal binding, folding and aggregation, and participate in diverse functions: epigenetic regulation of gene expression, RNA transport, cell cycle control, ubiquitination, signal transduction and organelle assembly.
Export Options
About this article
Cite this article as:
Kentsis A. and B. Borden L. K., Construction of Macromolecular Assemblages in Eukaryotic Processes and their Role in Human Disease: Linking RINGs Together, Current Protein & Peptide Science 2000; 1 (1) . https://dx.doi.org/10.2174/1389203003381478
DOI https://dx.doi.org/10.2174/1389203003381478 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
The Immunoproteasome as a Therapeutic Target for Hematological Malignancies
Current Cancer Drug Targets Melatonin and Melatoninergic Drugs as Therapeutic Agents: Ramelteon and Agomelatine, the Two Most Promising Melatonin Receptor Agonists
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Clinical Potential of VIP by Modified Pharmaco-kinetics and Delivery Mechanisms
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Stem Cells in Normal Liver and Cancer
Anti-Cancer Agents in Medicinal Chemistry Leukocyte P2 Receptors: A Novel Target for Anti-inflammatory and Antitumor Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Design of Fucoidan Functionalized - Iron Oxide Nanoparticles for Biomedical Applications
Current Drug Delivery Tuftsin – Properties and Analogs
Current Medicinal Chemistry Mediterrranean Diet and Health Biological Importance of Olive Oil
Current Pharmaceutical Design Hormetic Potential of Sulforaphane (SFN) in Switching Cells’ Fate Towards Survival or Death
Mini-Reviews in Medicinal Chemistry Proteolytic Cleavage of Notch: “HIT and RUN”
Current Molecular Medicine Proteomic Classification of Breast Cancer
Current Drug Targets Beyond the HapMap Genotypic Data: Prospects of Deep Resequencing Projects
Current Bioinformatics Effects of Fucoidan and Chemotherapeutic Agent Combinations on Malignant and Non-malignant Breast Cell Lines
Current Pharmaceutical Biotechnology Regulation of ABC Transporter Function Via Phosphorylation by Protein Kinases
Current Pharmaceutical Biotechnology Challenges and Opportunities for Clinical Research in the Middle East
Applied Clinical Research, Clinical Trials and Regulatory Affairs IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression
Current Drug Targets The Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification
Current Pharmaceutical Design Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs
Current Cancer Drug Targets Control of Inflammatory Bowel Disease and Colorectal Cancer by Synthetic Vitamin D Receptor Ligands
Current Medicinal Chemistry