Decreased susceptibility to calpains of v-FosFBR but not of v-FosFBJ or v-JunASV17 retroviral proteins compared with their cellular counterparts.
The c-Fos and c-Jun transcription factors are rapidly turned over in vivo. One of the multiple pathways responsible for their breakdown is probably initiated by calpains, which are cytoplasmic calcium-dependent cysteine proteases. The c-fos gene has been transduced by two murine oncogenic retroviruses called Finkel-Biskis-Jenkins murine sarcoma virus (FBJ-MSV) and Finkel-Biskis-Reilly murine sarcoma virus (FBR-MSV); c-jun has been transduced by the chicken avian sarcoma virus 17 (ASV17) retrovirus. Using an in vitro degradation assay, we show that the mutated v-FosFBR, but not v-FosFBJ or v-JunASV17, is resistant to calpains. This property raises the interesting possibility that decreased sensitivity to calpains might contribute to the tumorigenic potential of FBR-MSV by allowing greater accumulation of the protein that it encodes in infected cells. It has also been demonstrated that resistance to cleavage by calpains does not result from mutations that have accumulated in the Fos moiety of the viral protein but rather from the addition of atypical peptide motifs at its both ends. This observation raises the interesting possibility that homologous regions in viral and cellular Fos either display slightly different conformations or are differentially accessible to interacting proteins.
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AM
Institut de Génétique Moléculaire/UMR 9942, CNRS, BP5051, Route de Mende, 34033 Montpellier Cedex 01, France.
Carillo
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Pariat
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Piechaczyk
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D001358:Avian Sarcoma Viruses / Q000235:genetics / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000378:metabolism; D016759:Oncogene Protein p65(gag-jun) / Q000145:classification / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000145:classification / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D009053:Sarcoma Viruses, Murine / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D002154:Calpain; D002118:Calcium