Journal Article

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

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

1998

Overview

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.

• Publisher: Springer Science and Business Media LLC,Nature Publishing,Nature Publishing Group,Nature Publishing Group [1987-....]
• Subject: 3T3 Cells / 3T3 Cells Animals Blood Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cattle Cell Cycle Cells / [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology / Activator protein 1 / Animals / Biochemistry, Molecular Biology / Biological and medical sciences / Blood / c-Fos protein / c-Jun protein / Calcium-Calmodulin-Dependent Protein Kinases / Calcium-Calmodulin-Dependent Protein Kinases - metabolism / Cattle / Cell Cycle / Cell cycle, cell proliferation / Cell physiology / Cells, Cultured / Culture Media / Cultured Culture Media Cysteine Endopeptidases/metabolism Embryo / Cysteine Endopeptidases / Cysteine Endopeptidases - metabolism / Degradation / Embryo fibroblasts / Embryo, Mammalian / Fibroblasts / Fluorescent Antibody Technique, Indirect / Fundamental and applied biological sciences. Psychology / Indirect G0 Phase Ligases/biosynthesis/metabolism Mice Multienzyme Complexes/metabolism Proteasome Endopeptidase Complex Proto-Oncogene Proteins c-fos/metabolism Proto-Oncogene Proteins c-jun/metabolism S Phase Temperature Ubiquitin-Protein Ligases / Life Sciences / Ligases / Ligases - biosynthesis / Ligases - metabolism / Lysosomes / Mammalian Fluorescent Antibody Technique / Mice / Molecular and cellular biology / Multienzyme Complexes / Multienzyme Complexes - metabolism / Phase transitions / Proteasome Endopeptidase Complex / Proteasomes / Proteinase inhibitors / Proteins / Proto-Oncogene Proteins c-fos / Proto-Oncogene Proteins c-fos - metabolism / Proto-Oncogene Proteins c-jun / Proto-Oncogene Proteins c-jun - metabolism / Resting Phase, Cell Cycle / S Phase / Temperature / Transcription factors / Ubiquitin / Ubiquitin-Protein Ligases