[The C-Jun oncoprotein].

Abstract

Jun and Fos are major components of the transcriptional complex AP-1 (Activator Protein-1), a collection of dimeric transcriptional activators composed of members of the Jun and Fos family of bZIP proteins, that bind to a common site known as TRE (TPA Responsive Element) or the AP-1 site. Transcription of c-jun is rapidly induced by exposure to different extra-cellular signals like growth factors, cytokines, tumor promoters (TPA), UV and other DNA-damaging agents. Transcriptional activation 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 of AP-1-dependent genes. Modifications of c-Jun include dephosphorylations, phosphorylations and oxydo-reduction. The transcriptional activation by c-Jun is modulated by heterodimerization with other members of the bZIP family of proteins, and by transcriptional interference with other transcription factors like some members of the hormone nuclear receptors, or MyoD. AP-1 is tightly associated to both the control of cell proliferation and the oncogenic process. Constitutive activation of AP-1 leads to cell transformation in vitro, probably due to the accumulation of homodimeric c-Jun:c-Jun complexes. This hypothesis has been directly confirmed by constructing c-Jun hybrid proteins capable to form only homodimers. Deregulated expression of such proteins efficiently transforms primary cells in culture. These hybrid proteins constitute a powerful tool in order to identify new cellular functions AP-1-dependent, involved in the control of cell proliferation.