Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain.
The role of the ubiquitin-dependent proteolysis system in c-Jun breakdown was investigated. Using in vitro experiments and a novel in vivo assay that utilizes molecularly-tagged ubiquitin and c-Jun proteins, it was shown that c-Jun, but not its transforming counterpart, retroviral v-Jun, can be efficiently multiubiquitinated. Consistently, v-Jun has a longer half-life than c-Jun. Mutagenesis experiments indicate that the reason for the escape of v-Jun from multiubiquitination and its resulting stabilization is the deletion of the delta domain, a stretch of 27 amino acids that is present in c-Jun but not in v-Jun. c-Jun sequences containing the delta domain, when transferred to the bacterial beta-galactosidase protein, function as a cis-acting ubiquitination and degradation signal. The correlation between transforming ability and the escape from ubiquitin-dependent degradation described here suggests a novel route to oncogenesis.
Treier
M
M
European Molecular Biology Laboratory, Differentiation Programme, Heidelberg, Federal Republic of Germany.
Staszewski
L M
LM
Bohmann
D
D
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D004252:DNA Mutational Analysis; D010450:Endopeptidases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D016759:Oncogene Protein p65(gag-jun); D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D014452:Ubiquitins; D010450:Endopeptidases; D008025:Ligases; D008239:Lysine