UBIQUITIN-DEPENDENT C-JUN DEGRADATION IN-VIVO IS MEDIATED BY THE DELTA-DOMAIN

The role of the ubiquitin-dependent proteolysis system in c-Jun breakd own was investigated. Using in vitro experiments and a novel in vivo a ssay that utilizes molecularly-tagged ubiquitin and c-Jun proteins, it was shown that c-Jun, but not its transforming counterpart, retrovira l v-Jun, can be efficiently multiubiquitinated. Consistently, v-Jun ha s a longer half-life than c-Jun. Mutagenesis experiments indicate that the reason for the escape of v-Jun from multiubiquitination and its r esulting 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 seq uences containing the delta domain, when transferred to the bacterial beta-galactosidase protein, function as a cis-acting ubiquitination an d degradation signal. The correlation between transforming ability and the escape from ubiquitin-dependent degradation described here sugges ts a novel route to oncogenesis.