The AP-1 family of transcription factors participates in almost any program of gene expression, in cell proliferation, in apoptosis, in numerous types of differentiation, in cancer and autoimmune disease. Enhanced understanding of AP-1 function has significant scientific benefit and important implications for the development of inhibitory drugs and technological innovations in the healthcare industry. It is of utmost importance to dissect the molecular functions of the AP-1 factors, to study how physiologic regulators affect these functions and to then design strategies of intervention for appropriate pathologies. Due to the complexity of the AP-1 family and the need to dissect the specific role of single members of the family by mouse genetics it is mandatory to approach this theme as a collaboration of several laboratories. The participant to this research-training network together have already generated gene disruption of most of the AP-1 members and characterized their phenotypes. The availability of mouse models and highly informative in vitro systems to study specific aspects of physiological and pathological processes represent a unique tool to fully understand the role of each member of the family. Objectives of the present proposal are the dissection of AP-1 function with the aim of mouse genetics and in vitro analysis of cell mutants. First, the generation of a second generation of mutant and transgenic animals to answer to specific questions raised by the increased knowledge. Second, derive specific primary cell and cell lines lacking single AP-1 genes or expressing specific AP- I dimmers. Third, analyze in reconstituted in vitro models the role of AP-1 factors in differentiation pathways cell cycle progression or cell transformation. Fourth, identification of new AP-1 target genes by gene expression analysis performed with mutant cell clones using the micro array technology and with proteomic analysis. Fifth, functional analysis of relevant