Regulation of AP-1 Activity by TGF

The activator protein-1 (AP-1) transcriptional complex is composed of DNA binding proteins belonging to the Jun and Fos proto-oncogene families, which play an important role in cell proliferation and transformation (reviewed in ref . 1 ). AP-1 activity is required to stimulate many genes that are induced following growth factor and cytokine treatment, and also is required for transformation mediated by oncogenes such as ras (2 ). Members of the Jun family can homodimerize or heterodimerize with each other or Fos family members, which cannot bind DNA on their own. The dimerization, which is mediated by a leucine zipper motif, allows the complex to bind to a consensus DNA sequence 5′-TGA G/C TCA-3′, termed an AP-1 site. This same sequence was found in several 12-O -tetradecanoylphorbol-13-acetate (TPA)-responsive genes and, hence, is also designated a TRE or TPA-responsive element. Heterodimers can form between c-Jun and ATF-2, a member of the CREB (CRE binding) protein family, allowing the complex to bind to CRE (cAMP regulatory element) sites, which differ from an AP-1 site by one nucleotide (3 ,4 ).