ATF4-integrated stress response pathway

The ATF4-integrated stress response (ISR) pathway centers on Activating Transcription Factor 4 (ATF4), a basic leucine zipper (bZIP) transcription factor that acts as a master regulator of cellular adaptation to various stresses. The ISR is triggered by diverse cellular insults, including amino acid deprivation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. These stresses converge on the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), which selectively enhances translation of ATF4 mRNA. Once translated, ATF4 translocates to the nucleus where it binds C/EBP–ATF response elements (CAREs), also known as amino acid response elements (AAREs), in target gene promoters. The pathway regulates genes involved in amino acid metabolism, autophagy, redox homeostasis, apoptosis, and mitochondrial function. It plays roles in cancer progression, neurodegeneration, and diseases linked with mitochondrial dysfunction.

Other names

Activating Transcription Factor 4-integrated stress responseISR pathway