DECREASED SUSCEPTIBILITY TO CALPAINS OF V-FOS(FBR) BUT NOT OF V-FOS(FBJ) OR V-JUN(ASV17) RETROVIRAL PROTEINS COMPARED WITH THEIR CELLULAR COUNTERPARTS

The c-Fos and c-Jun transcription factors are rapidly turned over in v ivo. One of the multiple pathways responsible for their breakdown is p robably 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 vir us (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 mu tated v-Fos(FBR), bat not v-Fos(FBJ) or v-Jun(ASV17), is resistant to calpains. This property raises the interesting possibility that decrea sed sensitivity to calpains might contribute to the tumorigenic potent ial of FBR-MSV by allowing greater accumulation of the protein that it encodes in infected cells. It has also been demonstrated that resista nce to cleavage by calpains does not result from mutations that have a ccumulated 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 a nd cellular Fos either display slightly different conformations or are differentially accessible to interacting proteins.