AP1

AP-1, or Activator Protein 1, is a family of dimeric transcription factors that regulate gene expression in response to a variety of stimuli. The canonical AP-1 complex is a heterodimer composed of Fos and Jun family members, such as c-Fos and c-Jun, though alternative dimers including other Fos or Jun proteins can form homodimers or heterodimers. All AP-1 proteins are basic leucine zipper (bZIP) transcription factors that bind DNA as dimers.

AP-1 recognizes the 5'-TGAC/GTCA-3' motif, known as the AP-1 site or the TRE (TPA-responsive element), typically located within promoters and enhancers of target genes. DNA-binding affinity and transcriptional activity are influenced by the specific dimer composition and the chromatin context.

Activation of AP-1 is mainly controlled by mitogen-activated protein kinase (MAPK) signaling pathways, including JNK, ERK, and p38. Phosphorylation of c-Jun by JNK enhances transcriptional activity; c-Fos is an immediate-early gene whose expression is rapidly induced by growth factors, stress, and other stimuli. The composition of the dimer determines target selectivity and regulatory outcomes, enabling AP-1 to act as an activator or, in some contexts, a repressor.

AP-1 regulates genes involved in cell proliferation, differentiation, apoptosis, immune responses, and inflammation, contributing to development, tissue remodeling, and responses to cellular stress. Dysregulation of AP-1 activity is linked to cancer and inflammatory diseases. Therapeutic approaches sometimes target AP-1 signaling to modulate pathological gene expression.