Figure 1

WFS1 is a key element of the ER stress activated signalling cascade, called the unfolded protein response (UPR). WFS1 regulates ATF6 protein through the ubiquitin-proteasone pathway, stabilizing and enhancing the function of its E3 ligase, HRD1 and acts as a negative regulator of this pathway. The E3 ubiquitin ligase HRD1 is found in the endoplasmic reticulum membrane and is involved in endoplasmic reticulum-associated degradation. In response to ER stress, the cleaved form of ATF6 translocates to the nucleus. The non-cleaved form of ATF6 is degraded by the ubiquitin-proteasome pathway to prevent the hyperactivation of the UPR.