1887

Abstract

Calreticulin (CRT) is an endoplasmic reticulum (ER) Ca²+ binding chaperone, which regulates many of cellular processes. Previous work from our lab showed loss of CRT leads to increased resistance to apoptosis. We also showed loss of CRT leads to increased AKT phosphorylation and activation of the proteosome activity. Thus we hypothesized that in the absence of CRT function, NFκB signaling is activated leading to enhanced resistance to apoptosis of these cells. Wild type and CRT knockout mouse embryonic fibroblast were used to examine changes in the NFκB signaling pathway. Reporter gene assays showed a significant reduction in the basal NFκB transcriptional activity. Activation of NFκB with lipopolysaccharide increased the transcriptional activity of NFκB in both the cells, however, the transcriptional activity of NFκB was still significantly lower in the CRT deficient cells as compared to the wild type cells. Our immunocytochemical staining showed a delay in the translocation of NFκB p65 to the nucleus of CRT deficient cells after lipopolysaccharide treatment. We also observed an increase in the level of IκB and phospho-IκB accumulation in CRT deficient cells after lipopolysaccharide treatment. We conclude that in the absence of CRT NFκB signaling is inhibited due to decreased IκB degradation and decreased NFκB p65 nuclear translocation.

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/content/papers/10.5339/qfarf.2012.BMP98
2012-10-01
2019-12-15
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