Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis

Jun:Fos and Jun:ATF complexes represent two classes of AP-1 dimers that (1) preferentially bind to, either heptameric or octameric AP-1 binding sites, and (2) are differently regulated by cellular signaling pathways and oncog ene products. To discriminate between the functions of Jun:Fos, Jun: ATF an d Jun:Jun, mutants were developed that restrict the ability of Jun to dimer ize either to itself, or to Fos(-like) or ATF(-like) partners. Introduction of these mutants in chicken embryo fibroblasts shows that Jun:Fra2 and Jun :ATF2 dimers play distinct, complementary roles in in vitro oncogenesis by inducing either anchorage independence or growth factor independence, respe ctively. v-Jun:ATF2 rather than v-Jun:Fra2 triggers the development of prim ary fibrosarcomas in the chicken wing. Genes encoding extracellular matrix components seem to constitute an important subset of v-Jun:ATF2-target gene s. Repression of the matrix component SPARC by Jun is essential for the ind uction of fibrosarcomas, Avian primary cells transformed by either Jun:Fra2 or Jun:ATF2 thus provide powerful tools for the investigation of the downs tream pathways involved in oncogenesis, Further genetic studies with Jun di merization mutants will be required to be precise and extend the specific r oles of the Jun:Fos and Jun:ATF dimers during cancer progression in avian a nd mammalian systems.