ATF4 is a basic leucine zipper (bZIP) transcription factor that binds to specific DNA sequences to regulate the transcription of target genes . It is involved in the unfolded protein response (UPR), a cellular stress response related to the ER . Under stress conditions, ATF4 is upregulated and activates genes that help the cell adapt and survive .
ATF4 is a key player in the cellular stress response. It helps cells cope with ER stress by regulating the expression of genes involved in protein folding, antioxidant responses, and amino acid metabolism . In addition, ATF4 is involved in the regulation of ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation . The dual role of ATF4 in promoting cell survival and ferroptosis highlights its complex function in cellular stress responses .
ATF4 has been implicated in various diseases, including cancer, neurodegenerative disorders, and metabolic diseases . In cancer, ATF4 can either promote or inhibit tumor growth depending on the context . Its role in neurodegenerative diseases is linked to its function in managing oxidative stress and protein misfolding .
Recent research has focused on understanding the genome-wide binding sites of ATF4 and its interaction with genetic variants associated with various traits and diseases . For example, studies have identified single-nucleotide polymorphisms (SNPs) that affect ATF4-mediated transcriptional activation, providing insights into the molecular mechanisms underlying these genetic associations .