title: Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase.
abstract: Ubiquitination of key cellular regulatory proteins marks them for efficient degradation via the proteasome pathway. The delta domain of c-jun is essential for its ubiquitination and also for the activating phosphorylation of neighboring serines by the stress activated jun-N-terminal kinases (JNK). Using an in vitro model system we demonstrate that JNK is among the hydrophobic binding proteins that target c-jun for efficient ubiquitination. Immunodepletion of JNK markedly inhibits c-jun ubiquitination. Conversely, c-jun ubiquitination is increased by adding purified JNK2 or extracts prepared from cells transfected with JNK2. Although c-jun ubiquitination is enhanced by JNK, the phosphorylation of c-jun on Ser73 by JNK protects c-jun from ubiquitination and prolongs its half-life. The dual activity of JNK in targeting c-jun for ubiquitination or in protecting c-jun from entering this pathway via phosphorylation points to the role of JNK in the control of c-jun stability in cells exposed to environmental stress or inflammatory cytokines.
authors.affiliation: Molecular Carcinogenesis Program, American Health Foundation, Valhalla, New York 10595, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Fuchs
authors.forename: L
authors.initials: L
authors.lastname: Dolan
authors.forename: R J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Z
authors.initials: Z
authors.lastname: Ronai
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D014452:Ubiquitins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases