Evasion from proteasomal degradation by mutated Fos proteins expressed from FBJ-MSV and FBR-MSV osteosarcomatogenic retroviruses.
c-Fos proto-oncoprotein is highly unstable, which is crucial for rapid gene expression shut-off and control of its intrinsic oncogenic potential. It is massively degraded by the proteasome in vivo in various situations. Although there is evidence that c-Fos can be ubiquitinylated in vitro, the unambiguous demonstration that ubiquitinylation is necessary for recognition and subsequent hydrolysis by the proteasome in vivo is still lacking. Moreover, genetic analysis have also indicated that c-Fos can be addressed to the proteasome via different mechanisms depending on the conditions studied. c-Fos has been transduced by two murine osteosarcomatogenic retroviruses under mutated forms which are more stable and more oncogenic. The stabilization is not simply accounted for by simple deletion of a C-terminal c-Fos destabilizer but, rather, by a complex balance between opposing destabilizing and stabilizing mutations. Though mutations in viral Fos proteins confer full resistance to proteasomal degradation, stabilization is limited because mutations also entail sensitivity to (an) unidentified proteolytic system(s). This observation is consistent with the idea that Fos-expressing viruses have evolved gene expression controls that avoid high protein accumulation-linked apoptosis.
Acquaviva
Claire
C
Institut de Génétique Moléculaire de Montpellier, UMR5535/IFR24, 1919, route de Mende, Montpellier, France.
Bossis
Guillaume
G
Ferrara
Patrizia
P
Brockly
Frédérique
F
Jariel-Encontre
Isabelle
I
Piechaczyk
Marc
M
D000818:Animals; D002472:Cell Transformation, Viral; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D012516:Osteosarcoma / Q000378:metabolism / Q000821:virology*; D046988:Proteasome Endopeptidase Complex; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism* / Q000502:physiology; D014764:Viral Proteins
D009097:Multienzyme Complexes; D016760:Proto-Oncogene Proteins c-fos; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex