Abstract
Nuclear receptors (NRs) regulate and coordinate multiple processes by integrating internal and external signals, thereby maintaining homeostasis in front of nutritional, behavioral and environmental challenges. NRs exhibit strong similarities in their structure and mode of action: by selective transcriptional activation or repression of cognate target genes, which can either be controlled through a direct, DNA binding-dependent mechanism or through crosstalk with other transcriptional regulators, NRs modulate the expression of gene clusters thus achieving coordinated tissue responses. Additionally, non genomic effects of NR ligands appear mediated by ill-defined mechanisms at the plasma membrane. These effects mediate potential therapeutic effects as small lipophilic molecule targets, and many efforts have been put in elucidating their precise mechanism of action and pathophysiological roles. Currently, numerous nuclear receptor ligand analogs are used in therapy or are tested in clinical trials against various diseases such as hypertriglyceridemia, atherosclerosis, diabetes, allergies and cancer and others.
Keywords: transcriptional regulation, nuclear receptors, coactivators, corepressors, structure, DNA binding-dependent mechanism, nuclear receptor ligand analogs, architecture and functional behavior, transactivation and transrepression activities, phylogenetic, DNA-binding domain (DBD), P-box, vicinity
Current Topics in Medicinal Chemistry
Title: General Molecular Biology and Architecture of Nuclear Receptors
Volume: 12 Issue: 6
Author(s): Michal Pawlak, Philippe Lefebvre and Bart Staels
Affiliation:
Keywords: transcriptional regulation, nuclear receptors, coactivators, corepressors, structure, DNA binding-dependent mechanism, nuclear receptor ligand analogs, architecture and functional behavior, transactivation and transrepression activities, phylogenetic, DNA-binding domain (DBD), P-box, vicinity
Abstract: Nuclear receptors (NRs) regulate and coordinate multiple processes by integrating internal and external signals, thereby maintaining homeostasis in front of nutritional, behavioral and environmental challenges. NRs exhibit strong similarities in their structure and mode of action: by selective transcriptional activation or repression of cognate target genes, which can either be controlled through a direct, DNA binding-dependent mechanism or through crosstalk with other transcriptional regulators, NRs modulate the expression of gene clusters thus achieving coordinated tissue responses. Additionally, non genomic effects of NR ligands appear mediated by ill-defined mechanisms at the plasma membrane. These effects mediate potential therapeutic effects as small lipophilic molecule targets, and many efforts have been put in elucidating their precise mechanism of action and pathophysiological roles. Currently, numerous nuclear receptor ligand analogs are used in therapy or are tested in clinical trials against various diseases such as hypertriglyceridemia, atherosclerosis, diabetes, allergies and cancer and others.
Export Options
About this article
Cite this article as:
Pawlak Michal, Lefebvre Philippe and Staels Bart, General Molecular Biology and Architecture of Nuclear Receptors, Current Topics in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/156802612799436641
DOI https://dx.doi.org/10.2174/156802612799436641 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Type I Interferons: Ancient Peptides with Still Under-Discovered Anti-Cancer Properties
Protein & Peptide Letters Retraction Notice: Clinical Strategies for Preventing Postoperative Nausea and Vomiting After Middle Ear Surgery in Adult Patients
Current Drug Safety Reconceptualizing Adult Neurogenesis: Role for Sphingosine-1-Phosphate and Fibroblast Growth Factor-1 in Co-Ordinating Astrocyte-Neuronal Precursor Interactions
CNS & Neurological Disorders - Drug Targets Cancer Stem Cell Markers in Nasopharyngeal Carcinoma and Its Relevance for Therapy
Current Traditional Medicine Studies of NVP-BEZ235 in Melanoma
Current Cancer Drug Targets The Leptin System: A Potential Target for Sepsis Induced Immune Suppression
Endocrine, Metabolic & Immune Disorders - Drug Targets Discovery of Novel CYP17 Inhibitors for the Treatment of Prostate Cancer with Structure-Based Drug Design
Letters in Drug Design & Discovery New Perspectives in the Treatment of Cushings Syndrome
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Regulation of Hepatic Cytochromes P450 by Lipids and Cholesterol
Current Drug Metabolism Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Immunomodulatory Roles of VIP and PACAP in Models of Multiple Sclerosis
Current Pharmaceutical Design Genetics, Structure, Function, Mode of Actions and Role in Cancer Development of CYP17
Anti-Cancer Agents in Medicinal Chemistry Natural Products as Aromatase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry The Emerging Role of Metabotropic Glutamate Receptors in the Pathophysiology of Chronic Stress-Related Disorders
Current Neuropharmacology Adrenal Hyperandrogenism and Polycystic Ovary Syndrome
Current Pharmaceutical Design Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Current Neuropharmacology Application of Monoclonal Antibodies as Cancer Therapy in Solid Tumors
Current Clinical Pharmacology Targeting the RAS Signaling Pathway in Malignant Hematologic Diseases
Current Drug Targets Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-Up in Three Families
Endocrine, Metabolic & Immune Disorders - Drug Targets