Fos family protein degradation by the proteasome

Gomard, T.; Jariel-Encontre, I.; Basbous, J.; Bossis, G.; Mocquet-Torcy, G.; Piechaczyk, M.

Biochem Soc Trans

2008-10 / vol 36 / pages 858-63


c-Fos proto-oncoprotein defines a family of closely related transcription factors (Fos proteins) also comprising Fra-1, Fra-2, FosB and DeltaFosB, the latter two proteins being generated by alternative splicing. Through the regulation of many genes, most of them still unidentified, they regulate major functions from the cell level up to the whole organism. Thus they are involved in the control of proliferation, differentiation and apoptosis, as well as in the control of responses to stresses, and they play important roles in organogenesis, immune responses and control of cognitive functions, among others. Fos proteins are intrinsically unstable. We have studied how two of them, c-Fos and Fra-1, are degraded. Departing from the classical scenario where unstable key cell regulators are hydrolysed by the proteasome after polyubiquitination, we showed that the bulk of c-Fos and Fra-1 can be broken down independently of any prior ubiquitination. Certain conserved structural domains suggest that similar mechanisms may also apply to Fra-2 and FosB. Computer search indicates that certain motifs shared by the Fos proteins and putatively responsible for instability are found in no other protein, suggesting the existence of degradation mechanisms specific for this protein family. Under particular signalling conditions, others have shown that a part of cytoplasmic c-Fos requires ubiquitination for fast turnover. This poses the question of the multiplicity of degradation pathways that apply to proteins depending on their intracellular localization.

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Animals; Mice; Amino Acid Sequence; Molecular Sequence Data; Sequence Alignment; Proteasome Endopeptidase Complex/*metabolism; Ubiquitin/metabolism; Proto-Oncogene Proteins c-fos/genetics/*metabolism; Extracellular Signal-Regulated MAP Kinases/genetics/metabolism; Mitogen-Activated Protein Kinases/genetics/metabolism

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