THE C-JUN ONCOPROTEIN

Jun and Fos are major components of the transcriptional complex AP-1 ( Activator Protein-1), a collection of dimeric transcriptional activato rs composed of members of the Jun and Fos family of bZIP proteins, tha t bind to a common site known as TRE (TPA Responsive Element) or the A P-1 site. Transcription of c-jun is rapidly induced by exposure to dif ferent extra-cellular signals like growth factors, cytokines, tumor pr omoters (TPA), UV and other DNA -damaging agents. Transcriptional acti vation of c-jun is a two step mechanism. First, the pre-existing c-Jun protein is activated by posttranscriptional modifications, and second , modified c-Jun activates its own transcription, and the expression o f AP-1-dependent genes. Modifications of c-Jun include dephosphorylati ons, phosphorylations and oxydo-reduction. The transcriptional activat ion by c-Jun is modulated by heterodimerisation with other members of the bZIP family of proteins, and by transcriptional interference with other transcription factors like some members of the hormone nuclear r eceptors, or MyoD. AP-1 is tightly associated to both the control of c ell proliferation and the oncogenic process. Constitutive activation o f AP-1 leads to cell transformation in vitro, probably due to the accu mulation of homodimeric c-Jun:c-Jun complexes. This hypothesis has bee n directly confirmed by constructing c-Jun hybrid proteins capable to form only homodimers. Deregulated expression of such proteins efficien tly transforms primary cells in culture. These hybrid proteins constit ute a powerful tool in order to identify new cellular functions AP-1-d ependent, involved in the control of cell proliferation.