ATF6 - Endoplasmic reticulum stress

The endoplasmic reticulum (ER) stress occurs when the folding capacity of the ER becomes saturated. Persistent ER stress can fuel oncogenic pathways and cause several metabolic alterations. Also, an malfunctioning ER promothes the the accumulation of misfolded proteins, which is associated with cell aging.

One indicator of ER stress is the ER transmembrane protein ATF6, involved in the unfolded protein response. When misfolded proteins accumulate in the ER, the ATF6 protein is cleaved and directed to the cell nucleus, where it acts as a transcription factor to promote the transcription of ER chaperones genes. This translocation can be observed and measured in cells, indicating the ER stress response.