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.
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