Endoplasmic Reticulum To Nucleus Signalling 2 (ERN2)

In mammalian cells, the UPR induces transcription of genes encoding ER protein chaperones, such as BiP. ER stress activates other pathways, including the expression of the CHOP transcription factor, and is also linked to the development of programmed cell death. In S. cerevisiae, the ER-associated transmembrane Ire1 (inositol-requiring-1)/Ern1 protein kinase is the UPR proximal sensor that monitors the status of unfolded protein inside the ER lumen. Like yeast Ire1, the predicted mouse Ern2 protein is a putative type I transmembrane protein and contains a C-terminal kinase/endonuclease effector domain. The C-terminal regions of Ire1 and Ern2 are 40% identical. When expressed in mammalian cells, Ern2 localized to the ER. Overexpression activated both BiP and CHOP expression, and also led to the development of programmed cell death.