Figure 3

Scheme illustrating endoplasmic reticulum (ER) stress-mediated activation of SND1 promoter activity. SND1 is an ER stress target gene. The three families of signal transducers IRE1, PERK and ATF6 sense the protein folding conditions of the ER and transmit that information, resulting in production of transcription regulators that enter the nucleus to drive transcription of UPR target genes. The ER chaperone GRP78 is normally bound to these ER stress sensors and keeps them inactive. By blocking protein N-glycosylation and disturbing Ca²⁺ homeostasis in the ER, tunicamycin and thapsigargin promote accumulation of misfolded proteins that sequester GRP78, leading to the concerted activation of the three stress sensors, which work alone or together to activate UPR target genes. Simultaneously, mRNA translation is globally inhibited and a subset of cellular mRNAs is translationally silenced by sequestration into stress granules. SND1 promoter activity is enhanced by thapsigargin, tunicamycin or ectopic expression of ATF6.