Activating transcription factor 4 (ATF4)

Activating transcription factor 4 (ATF4) is a member of the basic leucine zipper (bZIP) family of transcription factors that plays a central role in cellular stress responses, particularly in adaptation to metabolic and oxidative stress. ATF4 is mostly activated by phosphorylation of eIF2α in response to a range of stressors, including ER stress, nutritional deprivation, hypoxia. ATF4 regulates the transcription of genes involved in amino acid metabolism, redox homeostasis, cell cycle arrest, and apoptosis. It largely acts through heterodimerization with other bZIP family proteins, rather than as a homodimer, which imparts its broad regulatory versatility. ATF4 has been implicated in various pathological processes, including cancer progression (e.g., glioblastoma), neurodegeneration, and muscle atrophy, making it a relevant therapeutic target[1][2][3][5]. Drugs such as loperamide and withaferin A can modulate ATF4 pathways to induce autophagy or apoptosis in cancer cells. ATF4 is sometimes referred to as CREB-2 and interacts with cAMP response elements (CRE) on DNA to modulate gene expression in response to stress[2][3][1].

Other names

CREB-2cAMP response element binding protein 2Tax-responsive enhancer element B67

Inducing or modulating integrated stress response (ISR) through eIF2α phosphorylation and ATF4-dependent gene expression; Inducing apoptosis and autophagy by activating ER stress pathways; Promoting metabolic reprogramming and adaptive survival in cancer cells