Ubiquitin-Dependent c-Jun Degradation In Vivo Is Mediated by the 8 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 8 domain, a stretch of 27 amino acids that is present in c-Jun but not in v-Jun, c-Jun sequences containing the 6 domain, when transferred to the bacterial I~-galactosidase protein, function as a cis-acting ubiquitination and degradation signal. The correlation between transforming ability and the escape from ubiquitindependent degradation described here suggests a novel route to oncogenesis.