Activating transcription factor 3 (ATF3) (ATF3)

Activating transcription factor 3 (ATF3) is a member of the basic leucine zipper (bZIP) family of transcription factors and serves as a critical hub in the cellular adaptive stress response network. Under normal physiological conditions, ATF3 is expressed at very low levels, but it is rapidly and robustly induced by various stressors, including DNA damage, oxidative stress, endoplasmic reticulum stress, and pro-inflammatory cytokines (UniProt, 2024). Once induced, ATF3 can function as either a transcriptional repressor or activator, depending on its homodimerization or heterodimerization with other bZIP proteins like c-Jun or JUNB. In human disease, ATF3 plays a complex, context-dependent role; it is often characterized as a tumor suppressor in certain cancers like glioblastoma but can promote metastasis and cell survival in others, such as breast cancer (PubMed, 2023). While no drugs currently target ATF3 directly in clinical practice, several small molecules and natural compounds, including NSAIDs and polyphenols, are known to modulate its expression to exert anti-inflammatory or anti-tumor effects. Its role as a master regulator of stress makes it a significant target for therapeutic intervention in inflammatory disorders and metabolic diseases like type 2 diabetes (NIH, 2024).

Other names

Cyclic AMP-dependent transcription factor ATF-3cAMP-dependent transcription factor ATF-3LRG-21

Modulation of transcriptional activity and gene expression levels