Degradation of cellular and viral Fos proteins

c-Fos proto-oncoprotein is a short-lived transcription factor with oncogeni c potential. We have shown that it is massively degraded by the proteasome in vivo under various experimental conditions. Other proteolytic sytems inc luding lysosomes and calpains, might, however, also marginaly operate on it . Although there is evidence that c-Fos can be ubiquitinylated in vitro, th e unambiguous demonstration that ubiquitinylation is necessary for its addr essing to the proteasome in vivo is still lacking. c-Jun, one of the main d imerization partners of c-Fos within the AP-1 transcription complex, is als o an unstable protein. Its degradation is clearly proteasome- and ubiquitin -dependent in vivo. Interestingly, several lines of evidence indicate that the addressing of c-Fos and c-Jun to the proteasome is, at least in part, g overned by different mechanisms, c-Fos has been transduced by two murine os teosarcomatogenic retroviruses under mutated forms which are more stable an d more oncogenic. The stabilization is not simply accounted for by simple d eletion of c-Fos main destabilizer but, rather, by a complex balance betwee n opposing destabilizing and stabilizing mutations. Though mutations in vir al Fos proteins confer full resistance to proteasomal degradation, stabiliz ation is limited because mutations also entail sensitivity to an unidentifi ed proteolytic system. This observation is consistent with the idea that Fo s-expressing viruses have evolved to ensure control protein levels to avoid high protein accumulation-linked apoptosis. In conclusion, the unveiling o f the complex mechanism network responsible for the degradation of AP-1 fam ily members is still at its beginning and a number of issues regarding the regulation of this process and the addressing to the proteasome are still u nresolved. (C) 2001 Societe francaise de biochimie et biologie moleculaire / Editions scientifiques et medicales Elsevier SAS. All rights reserved.