| First Author | Massaeli H | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1843 |
| Issue | 11 | Pages | 2385-93 |
| PubMed ID | 24998604 | Mgi Jnum | J:218494 |
| Mgi Id | MGI:5617678 | Doi | 10.1016/j.bbamcr.2014.06.017 |
| Citation | Massaeli H, et al. (2014) Loss of calreticulin function decreases NFkappaB activity by stabilizing IkappaB protein. Biochim Biophys Acta 1843(11):2385-93 |
| abstractText | Transcription factor NFkappaB is activated by several processes including inflammation, endoplasmic-reticulum (ER) stress, increase in Akt signaling and enhanced proteasomal degradation. Calreticulin (CRT) is an ER Ca(2+)-binding chaperone that regulates many cellular processes. Gene-targeted deletion of CRT has been shown to induce ER stress that is accompanied with a significant increase in the proteasome activity. Loss of CRT function increases the resistance of CRT-deficient (crt-/-) cells to UV- and drug-induced apoptosis. Based on these reports we hypothesized that loss of CRT will activate NFkappaB signaling thus contributing to enhanced resistance to apoptosis. In contrast to our hypothesis, we observed a significant decrease in the basal transcriptional activity of NFkappaB in CRT-deficient cells. Treatment with lipopolysaccharide failed to increase the transcriptional activity of NFkappaB in the crt-/- cells to the same level as in the wt cells. Our data illustrate that the mechanism of decreased NFkappaB activity in CRT-deficient cells is mediated by a significant increase in IkappaB protein expression. Furthermore, we showed a significant increase in protein phosphatase 2A activity inhibition which resulted in decreased IkappaBalpha protein level in CRT-deficient cells. Based on our data we concluded that loss of CRT increases the stability of IkappaB protein thus reducing NFkappaB activity. |
