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 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Transforming Growth Factor-β: A Molecular Target for the Future Therapy of Glioblastoma
Current Pharmaceutical Design Targeting Breast Cancer Stem Cells: A Methodological Perspective
Current Stem Cell Research & Therapy Clinical Implications of COX-1 and / or COX-2 Inhibition for the Distal Gastrointestinal Tract
Current Pharmaceutical Design Reversal of Tumor Induced Dendritic Cell Paralysis: A Treatment Regimen Against Cancer
Current Immunology Reviews (Discontinued) Relationship Between the Chemokine Receptor CCR5 and Microglia in Neurological Disorders: Consequences of Targeting CCR5 on Neuroinflammation, Neuronal Death and Regeneration in a Model of Epilepsy
CNS & Neurological Disorders - Drug Targets Lipoxygenase Inhibitors as Cancer Chemopreventives: Discovery, Recent Developments and Future Perspectives
Current Medicinal Chemistry <i>In Vivo</i> Anti-Tumor Effects of Flavokawain A in 4T1 Breast Cancer Cell-Challenged Mice
Anti-Cancer Agents in Medicinal Chemistry 5-HT3 Receptors
Current Pharmaceutical Design Efficacy of PD-1 or PD-L1 Inhibitors and Central Nervous System Metastases in Advanced Cancer: A Meta-Analysis
Current Cancer Drug Targets The Application of Nanomaterials in Stem Cell Therapy for Some Neurological Diseases
Current Drug Targets Looking Beyond Inhibition of VEGF/mTOR: Emerging Targets for Renal Cell Carcinoma Drug Development
Current Clinical Pharmacology Opportunities and Challenges in Nano-structure Mediated Drug Delivery: Where Do We Stand?
Current Nanomedicine Psychoemotional Background of Temporomandibular Joint Dysfunction and Possible Drug Therapy
Letters in Drug Design & Discovery Lipid-based Nano-phytomedicines for Disease Treatment and Theranostic Applications
Current Nanomedicine Roles of Casein Kinase I η and δ in Gastrointestinal Cancers: Potential New Screening Markers and Drug Targets
Current Cancer Therapy Reviews (6-Bromo-1,4-dimethyl-9<i>H</i>-carbazol-3-yl-methylene)-hydrazine (Carbhydraz) Acts as a GPER Agonist in Breast Cancer Cells
Current Topics in Medicinal Chemistry Impact of Drug Metabolism/Pharmacokinetics and their Relevance Upon Traditional Medicine-based Cardiovascular Drug Research
Current Drug Metabolism Purine-Scaffold Hsp90 Inhibitors
Current Topics in Medicinal Chemistry Exosomes Harnessed as Nanocarriers for Cancer Therapy - Current Status and Potential for Future Clinical Applications
Current Molecular Medicine Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues
Anti-Cancer Agents in Medicinal Chemistry