Signaling of p53 expression by NF-κB during endoplasmic reticulum stress.

<p>Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum induces activation of multiple signaling pathways. Many studies have indicated that activation of IRE1, ATF6, and PERK represents the standard UPR pathways and turns on the expression of many downstream genes such as <i>GRP78</i>. ER stress induced caspase-12/caspase-9/caspase-3, PERK/ATF-4/CHOP, IRE1/Ask1/JNK, and PERK/eIF2α/NF-κB signaling pathways and then those pathways may alter cellular homeostasis by regulating multiple genes, resulting in regulation of cell death or survival. This pathway (indicated by <i>heavy arrows</i>) is demonstrated in this report. We demonstrated that induction of p53 expression is mediated by NF-κB during ER stress.