![conference banner](/images/conference-banner.jpeg)
Abstract
Nuclear Factor-kB (NF-kB), is a transcription factor composed of dimeric complexes of p50 (NF-kB1) or p52 (NF-kB2) usually associated with members of the Rel family (p65, c-Rel, Rel B) which have potent transactivation domains. Different combinations of NF-kB/Rel proteins bind distinct kB sites to regulate the transcription of different genes. In resting cells NF-kB resides in the cytoplasm in inactive form, complexed to members of a family of inhibitory proteins referred to as IkB. The bound IkB masks the NF-kB nuclear localization signal and thereby inhibits its nuclear transport. NF-kB can be activated by a variety of signals relevant to pathophysiology including inflammatory cytokines and bacterial lipopolysaccharides (LPS) as well as oxidative and fluid mechanical stress. Upon activation by these stimuli, IkB is phosphorylated and subsequently degraded. Phosphorylation targets IkB for ubiquitination and degradation by the 26S proteasome thus leading to NF-kB nuclear translocation. The same proteolytic pathway is involved in the processing of the p105 and p100 precursors to generate mature p50 and p52 subunits, respectively. Once in the nucleus, NF-kB is able to regulate the expression of many genes involved in the immune and inflammatory responses (i.e. inflammatory cytokines and adhesion molecules). Thus, new approaches to modulating NF-kB activation, and as a consequence inflammatory or metastatic processes, may take advantage of the selectivity of the ubiquitination and ATP-dependent proteolytic processes leading to IkB turnover. This review will analyze the current strategies aimed at interfering with NF-kB activation and will consider the ubiquitination system as a new selective target for the development of new anti-inflammatory therapies.
Keywords: Ubiquitin, Nuclear factor, transcription, matastatic, IKB inhibitor, Anti inflammatory, protesome, mutagenesis
Current Drug Targets
Title: The Ubiquitin-Dependent Proteolytic System and other Potential Targets for the Modulation of Nuclear Factor-kB (NF-kB)
Volume: 1 Issue: 4
Author(s): M. Magnani, R. Crinelli, M. Bianchi and A. Antonelli
Affiliation:
Keywords: Ubiquitin, Nuclear factor, transcription, matastatic, IKB inhibitor, Anti inflammatory, protesome, mutagenesis
Abstract: Nuclear Factor-kB (NF-kB), is a transcription factor composed of dimeric complexes of p50 (NF-kB1) or p52 (NF-kB2) usually associated with members of the Rel family (p65, c-Rel, Rel B) which have potent transactivation domains. Different combinations of NF-kB/Rel proteins bind distinct kB sites to regulate the transcription of different genes. In resting cells NF-kB resides in the cytoplasm in inactive form, complexed to members of a family of inhibitory proteins referred to as IkB. The bound IkB masks the NF-kB nuclear localization signal and thereby inhibits its nuclear transport. NF-kB can be activated by a variety of signals relevant to pathophysiology including inflammatory cytokines and bacterial lipopolysaccharides (LPS) as well as oxidative and fluid mechanical stress. Upon activation by these stimuli, IkB is phosphorylated and subsequently degraded. Phosphorylation targets IkB for ubiquitination and degradation by the 26S proteasome thus leading to NF-kB nuclear translocation. The same proteolytic pathway is involved in the processing of the p105 and p100 precursors to generate mature p50 and p52 subunits, respectively. Once in the nucleus, NF-kB is able to regulate the expression of many genes involved in the immune and inflammatory responses (i.e. inflammatory cytokines and adhesion molecules). Thus, new approaches to modulating NF-kB activation, and as a consequence inflammatory or metastatic processes, may take advantage of the selectivity of the ubiquitination and ATP-dependent proteolytic processes leading to IkB turnover. This review will analyze the current strategies aimed at interfering with NF-kB activation and will consider the ubiquitination system as a new selective target for the development of new anti-inflammatory therapies.
Export Options
About this article
Cite this article as:
Magnani M., Crinelli R., Bianchi M. and Antonelli A., The Ubiquitin-Dependent Proteolytic System and other Potential Targets for the Modulation of Nuclear Factor-kB (NF-kB), Current Drug Targets 2000; 1 (4) . https://dx.doi.org/10.2174/1389450003349056
DOI https://dx.doi.org/10.2174/1389450003349056 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response, and/or therapy ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Biologics and the Cardiovascular System: A Double-Edged Sword
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Histamine H4 Receptor: A Novel Therapeutic Target for Immune and Allergic Responses
Mini-Reviews in Medicinal Chemistry The Role of Minocycline in Ischemia-Reperfusion Injury: A Comprehensive Review of an Old Drug with New Implications
Recent Patents on Cardiovascular Drug Discovery An Update on Disease Modifying Antirheumatic Drugs
Inflammation & Allergy - Drug Targets (Discontinued) Plasminogen Activator Inhibitor-1 in Tumor Growth, Angiogenesis and Vascular Remodeling
Current Pharmaceutical Design Mast Cells in Allergic and Inflammatory Diseases
Current Pharmaceutical Design Methods for Evaluating Sensory, Affective and Cognitive Disorders in Neuropathic Rodents
Current Neuropharmacology Modulation of TNF Receptor Family Members to Inhibit Autoimmune Disease
Current Drug Targets - Inflammation & Allergy Synthesis and In-vitro Photodynamic Studies of the Superparamagnetic Chitosan Hydrogel/Chlorin E6 Nanocarriers
Medicinal Chemistry Clinical Pharmacokinetics of Ibuprofen Arginine
Current Clinical Pharmacology Cyclodextrins as Complexation Agents to Improve the Anti-inflammatory Drugs Profile: a Systematic Review and Meta-Analysis
Current Pharmaceutical Design Cytokines in the Pathogenesis of Chronic Obstructive Pulmonary Disease
Current Pharmaceutical Design The Brain-Immune-Gut Triangle: Innate Immunity in Psychiatric and Neurological Disorders
Current Immunology Reviews (Discontinued) Severe Autoimmune Hemolytic Anemia Complicating Treatment-naive Chronic Hepatitis C Infection: A Case Report
Cardiovascular & Hematological Disorders-Drug Targets Current and Future Pharmaceutical Therapy for Rheumatoid Arthritis
Current Pharmaceutical Design MMP-9, a Potential Target for Cerebral Ischemic Treatment
Current Neuropharmacology Alternate Strategies of Hsp90 Modulation for the Treatment of Cancer and Other Diseases
Current Topics in Medicinal Chemistry Targeting Signaling Pathways in Chronic Lymphocytic Leukemia
Current Cancer Drug Targets Effect of Simvastatin on Inflammatory Cytokines Balance in Air Pouch Granuloma Model
Inflammation & Allergy - Drug Targets (Discontinued) Adipokines, Metabolism and the Immune Response in the Regulation of Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents