PROTOONCOGENE C-FOS - A MOLECULAR GO-BETWEEN

Proto-oncogene c-fos codes for a transcription factor and belongs to the so-called <<immediate early response>> genes which are rapidly and transiently induced by numerous stimuli in a wide variety of cell types. It is currently envisioned as a <<master switch>> which allows the cell to manipulate a large number of interacting transduction pathways involved in processes as different as the control of the subtle balance between cell differentiation and proliferation, or probably the establishment of short-term memory. While a wealth of information has accumulated about this proto-oncogene it is, contrary to others, like myc or, ras, only rarely involved in spontaneous tumors. This is probably due to the existence of negative regulatory loops present at almost all steps governing its expression. Interestingly, the known viruses which have transduced c-fos have eliminated most of these negative regulatory elements and thus, by overproducing the protein, can give rise to cell transformation. However, belonging to a highly complex regulatory network and with the remarkable property of its protein to associate with a large number of partners including the jun family, it can be taken as a magnificent paradigm for the study of eukaryotic gene regulation. Starting from its modular promoter which allows the gene to respond very quickly to stimuli as diverse as growth factors, cAMP or ion influxes, down to its mRNA or protein which are rapidly degraded, and then back to the nucleus where the protein operates, the study of c-fos gene regulation has considerably contributed to our understanding of the strategies used by the cell to transform an external stimulus into a genetic program.