Differential directing of c-Fos and c-Jun proteins to the proteasome in serum-stimulated mouse embryo fibroblasts

Salvat, C.; Jariel-Encontre, I.; Acquaviva, C.; Omura, S.; Piechaczyk, M.


1998-07-23 / vol 17 / pages 327-37


c-Fos and c-Jun proteins are highly unstable transcription factors that heterodimerize within the AP-1 transcription complex. Their accumulation is transiently induced at the beginning of the G0-to-S phase transition in quiescent cells stimulated for growth. To address the mechanisms responsible for rapid clearance of c-Fos and c-Jun proteins under these experimental conditions, we have used the ts20 mouse embryo fibroblasts which express a thermosensitive mutant of the E1 enzyme of the ubiquitin pathway. The use of cell-permeant protease inhibitors indicates that both proteins are degraded by the proteasome and excludes any major contribution for calpains and lysosomes during the G0-to-S phase transition. Synchronisation of ts20 cells at the non permissive temperature blocks the degradation of c-Jun, indicating that this process is E1-dependent. In contrast, c-Fos is broken down according to an apparently E1-independent pathway in ts20 cells, although a role for ubiquitinylation in this process cannot be formally ruled out. Interestingly, c-Jun is highly unstable in c-Fos-null mouse embryo fibroblasts stimulated for growth. Taken together, these observations show that in vivo during a G0-to-S phase transition (i) the precise mechanisms triggering c-Fos and c-Jun directing to the proteasome are not identical, (ii) the presence of c-Fos is not an absolute prerequisite for the degradation of c-Jun and (iii) the degradation of c-Jun is not required for that of c-Fos.

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Animals; Cells, Cultured; Mice; Proto-Oncogene Proteins c-fos/*metabolism; Multienzyme Complexes/*metabolism; S Phase; Temperature; Cattle; Embryo, Mammalian; Fluorescent Antibody Technique, Indirect; Proto-Oncogene Proteins c-jun/*metabolism; *Cell Cycle; 3T3 Cells; Blood; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Culture Media; Cysteine Endopeptidases/*metabolism; G0 Phase; Ligases/biosynthesis/*metabolism; Proteasome Endopeptidase Complex; Ubiquitin-Protein Ligases

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