C-JUN NH2-TERMINAL KINASES TARGET THE UBIQUITINATION OF THEIR ASSOCIATED TRANSCRIPTION FACTORS

Regulatory proteins are often ubiquitinated, depending on their phosph orylation status as well as on their association with ancillary protei ns that serve as adapters of the ubiquitination machinery, We previous ly demonstrated that c-Jun is targeted for ubiquitination by its assoc iation with inactive c-Jun NH2-terminal kinase (JNK), Phosphorylation by activated JNK protects c-Jun from ubiquitination, thus by prolongin g its half-life, In the study reported here, we determined the ability of JNK to target ubiquitination of its other substrates (Elk1 and act ivating transcription factor 2 (ATF2)) and associated proteins (ATF2 a nd JunB), We demonstrate that phosphorylation by JNK protects ATF2, bu t not Elk1, from JNK-targeted ubiquitination. We also show that associ ation of inactive JNK with JunB or ATF2 is necessary to target them fo r ubiquitination, Unlike its targeting of c-Jun, JNK requires addition al cellular components, yet to be identified, to target the ubiquitina tion of ATF2., Elk1 is phosphorylated by JNK, but JNK neither associat es with nor targets Elk1 for ubiquitination. The implications for the dual role of JNK in the regulation of ubiquitination and stability of c-Jun, ATF2, and JunB in normally growing versus stressed cells are di scussed.