Differential directing of c-Fos and c-Jun proteins to the proteasome in serum-stimulated mouse embryo fibroblasts.
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.
Institut de Génétique Moléculaire, UMR5535, CNRS-1919, Montpellier, France.
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Salvat
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Jariel-Encontre
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Acquaviva
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Omura
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Piechaczyk
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002417:Cattle; D002453:Cell Cycle; D002478:Cells, Cultured; D003470:Culture Media; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004622:Embryo, Mammalian; D019084:Fluorescent Antibody Technique, Indirect; D008025:Ligases / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013696:Temperature; D044767:Ubiquitin-Protein Ligases
D003470:Culture Media; D009097:Multienzyme Complexes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D044767:Ubiquitin-Protein Ligases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases