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.
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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 |
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