The unfolded protein response (UPR) is a signaling cascade triggered by conditions that cause the accumulation of improperly folded proteins in the endoplasmic reticulum (ER). The ER stress response results in increased expression of genes containing the ER stress response element in their promoters and include the genes for ER chaperones, such as grp78 and ERp72. Parker et al. identified the molecular identity of the ER stress-response-element binding factor (ERSF) involved in regulating ER stress-responsive gene activity. ERSF is the ubiquitous transcriptional regulator TFII-I (best known for its role in activating TATA-less promoters), and its role in UPR is dependent on a consensus tyrosine phosphorylation site, and its activity is enhanced by interaction with the transcriptional regulator ATF6. UPR triggers an increase in TFII-I itself, suggesting a positive feedback system for up-regulation of ERSF genes. R. Parker, T. Phan, P. Baumeister, B. Roy, V. Cheriyath, A. L. Roy, A. S. Lee, Identification of TFII-I as the endoplasmic reticulum stress response binding element factor ERSF: Its autoregulation by stress and interaction with ATF6. Mol. Cell. Biol. 21 , 3220-3233 (2001). [Abstract] [Full Text]