Cyclic AMP-dependent transcription factor ATF3 (ATF3)

Cyclic AMP-dependent transcription factor ATF3, also known as Activating Transcription Factor 3, is a member of the basic leucine zipper (bZIP) family of transcription factors that serves as a critical hub in the cellular adaptive stress response. Under normal physiological conditions, ATF3 is expressed at very low levels but is rapidly induced by a wide array of stressors, including DNA damage, oxidative stress, and inflammatory cytokines (UniProt P18848). It functions primarily as a transcriptional repressor when forming homodimers, but it can also activate gene expression by forming heterodimers with other bZIP proteins such as c-Jun (PubMed: 17210610). In the context of human disease, ATF3 plays a complex, dual role; it can promote apoptosis and act as a tumor suppressor in certain cancers, while in others, it may facilitate metastasis and cell survival (PubMed: 29233075). Because of its involvement in regulating inflammatory pathways and metabolic homeostasis, ATF3 is an emerging therapeutic target for conditions ranging from chronic inflammation and type 2 diabetes to various malignancies (PubMed: 25118604). While direct small-molecule inhibitors are still in early development, several existing drugs and natural compounds, such as NSAIDs and polyphenols, are known to exert their effects through the modulation of ATF3 expression (PubMed: 15623514).

Other names

Activating transcription factor 3cAMP-dependent transcription factor ATF-3

ATF3 functions as a transcriptional regulator by binding to the cyclic AMP response element (CRE) site (5'-TGACGTCA-3') in the promoters of target genes. It can act as a homodimer to repress transcription or form heterodimers with other bZIP proteins like c-Jun or JUNB to activate or further modulate gene expression in response to cellular stress signals (UniProt P18848; PubMed: 17210610).