AP-1

Activating protein 1 (AP-1) is a dimeric transcription factor which serves as an integrator of numerous signals to regulate gene expression affecting cellular proliferation, differentiation, apoptosis, autophagy, inflammation, cellular migration, and neoplastic transformation. AP-1 is composed of proteins from several families whose common denominator is the possession of basic leucine-zipper (bZIP) domains that are essential for dimerization and DNA binding. Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) subfamilies are the major AP-1 proteins. ATF proteins ATF2, LRF1/ATF3, B-ATF, JDP1, and JDP2 are also components of AP-1, and the Maf subfamily, which includes c-Maf, MafB, MafA, MafG/F/K, and Nrl are considered to be close relatives which form heterodimers with Fos and Jun, and occupy AP-1 binding sites. Jun–Fos heterodimers bind preferentially to a heptamer consensus sequence known as the TPA responsive element (TRE; 5ʹ-TGA(C/G)TCA-3ʹ), whereas Jun-ATF dimers bind with higher affinity to another consensus sequence known as the cyclic AMP responsive element (CRE; 5ʹ- TGACGTCA -3ʹ). The seven Fos-Jun family members can form 18 different homo- and heterodimers. The composition of the dimers varies among different tissues, regulated by exposure to different stimuli, and determines specificity of the binding site and consequently the identity of activated genes (1). Increased diversity of AP-1 and consequently increased complexity, is also generated by the ability of “core AP-1 proteins” Jun and Fos to interact with other leucine-zipper-containing proteins, sometimes resulting in binding to novel DNA elements (2). Additional layers of complexity may stem from interactions of AP-1 components with structurally unrelated proteins which recruit them to other divergent binding sites on the DNA in order to regulate gene transcription (1).