Abstract
Regulator of calcineurin 1 (RCAN1) has been implicated in pathogenesis of neurodegeneration and various cancers. Recently, we showed that RCAN1 expression was elevated in Down Syndrome and Alzheimer’s disease and its expression transpose over induced neuronal apoptosis. As NF-κB is an important transcription factor involved in cell survival and RCAN1 played vital roles in cell viability, we examined whether NF-κB regulates RCAN1 gene expression. Our results here showed that the RCAN1 isoform 4 gene transcription can be activated by NF-κB signaling. NF-κB activated RCAN1 isoform 4 gene promoter. Luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation identified a NF-κB responsive element in the region of -576-554bp of the RCAN1 isoform 4 promoter. Activation of RCAN1 gene expression by NF-κB is independent from the calcineurin-NFAT signaling since the NF-κB responsive element was distinct from the NFAT binding sites that was previously identified in the region of -350-166bp. Indeed, activation of calcineurin-NFAT signaling decreased NF-κB transcriptional activity, while activation of NF-κB elevated NFAT transcriptional activity. RCAN1 isoform 4 gene transcription was repressed by its own protein expression in a negative feedback loop. Our findings about RCAN1 gene transcription regulated by NF-κB further supported the vital roles of RCAN1 in cellular functions and its involvement in AD pathogenesis.
Keywords: Gene transcription, nuclear factor-kappaB, negative feed back loop, RCAN.
Current Alzheimer Research
Title:Regulator of Calcineurin 1 Gene Transcription is Regulated by Nuclear Factor-kappaB
Volume: 11 Issue: 2
Author(s): Lanlan Zheng, Heng Liu, Pin Wang, Weihong Song and Xiulian Sun
Affiliation:
Keywords: Gene transcription, nuclear factor-kappaB, negative feed back loop, RCAN.
Abstract: Regulator of calcineurin 1 (RCAN1) has been implicated in pathogenesis of neurodegeneration and various cancers. Recently, we showed that RCAN1 expression was elevated in Down Syndrome and Alzheimer’s disease and its expression transpose over induced neuronal apoptosis. As NF-κB is an important transcription factor involved in cell survival and RCAN1 played vital roles in cell viability, we examined whether NF-κB regulates RCAN1 gene expression. Our results here showed that the RCAN1 isoform 4 gene transcription can be activated by NF-κB signaling. NF-κB activated RCAN1 isoform 4 gene promoter. Luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation identified a NF-κB responsive element in the region of -576-554bp of the RCAN1 isoform 4 promoter. Activation of RCAN1 gene expression by NF-κB is independent from the calcineurin-NFAT signaling since the NF-κB responsive element was distinct from the NFAT binding sites that was previously identified in the region of -350-166bp. Indeed, activation of calcineurin-NFAT signaling decreased NF-κB transcriptional activity, while activation of NF-κB elevated NFAT transcriptional activity. RCAN1 isoform 4 gene transcription was repressed by its own protein expression in a negative feedback loop. Our findings about RCAN1 gene transcription regulated by NF-κB further supported the vital roles of RCAN1 in cellular functions and its involvement in AD pathogenesis.
Export Options
About this article
Cite this article as:
Zheng Lanlan, Liu Heng, Wang Pin, Song Weihong and Sun Xiulian, Regulator of Calcineurin 1 Gene Transcription is Regulated by Nuclear Factor-kappaB, Current Alzheimer Research 2014; 11 (2) . https://dx.doi.org/10.2174/1567205010666131212114907
DOI https://dx.doi.org/10.2174/1567205010666131212114907 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
An Approach to Whole-Genome Identification of IRES Elements
Current Genomics Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) MicroRNA Dysregulation in Alzheimer's Disease
CNS & Neurological Disorders - Drug Targets MET and ALK as Targets for the Treatment of NSCLC
Current Pharmaceutical Design Interrelationships Between Cyclooxygenases and Aromatase: Unraveling the Relevance of Cyclooxygenase Inhibitors in Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Therapy Against Ischemic Injury
Current Pharmaceutical Design Cyclophilin A as a Target of Cisplatin Chemosensitizers
Current Cancer Drug Targets AMPA Receptor Antagonists: Potential Therapeutic Applications
Recent Patents on CNS Drug Discovery (Discontinued) NPFF2 Receptor is Involved in the Modulatory Effects of Neuropeptide FF for Macrophage Cell Line
Protein & Peptide Letters Epigenetics in Alzheimers Disease: a Focus on DNA Modifications
Current Pharmaceutical Design Modifying Radiation Damage
Current Drug Targets Oncologic Imaging End-Points for the Assessment of Therapy Response
Recent Patents on Anti-Cancer Drug Discovery Endothelial (Dys)Function in Lone Atrial Fibrillation
Current Pharmaceutical Design Neuronal Nitric Oxide Synthase and Sympathetic Nerve Activity in Neurovascular and Metabolic Systems
Current Neurovascular Research Pathophysiology of NASH: Perspectives for a Targeted Treatment
Current Pharmaceutical Design Modulators of the Vascular Endothelin Receptor in Blood Pressure Regulation and Hypertension
Current Molecular Pharmacology Biology and Impact of Signal Transducers and Activators of Transcription and Their Regulators as Targets in Cancer Therapy
Current Signal Transduction Therapy Distribution, Metabolism, Excretion and Toxicokinetics of Vitexin in Rats and Dogs
Current Pharmaceutical Analysis Novel Agents in the Management of Lung Cancer
Current Medicinal Chemistry Neurotrophins' Modulation by Olive Polyphenols
Current Medicinal Chemistry