title: COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation.
abstract: The oncoprotein c-Jun is a component of the activator protein-1 transcription factor complex, which is involved in cellular proliferation, transformation, and death. The stabilization of c-Jun is critically important for its function. The phosphorylation of c-Jun by c-Jun NH(2)-terminal kinase 1 and extracellular signal-regulated protein kinases reduces c-Jun ubiquitination resulting in increased stabilization of c-Jun. In this report, we showed that COOH-terminal Src kinase (CSK) binds with and phosphorylates c-Jun at Y26 and Y170. Phosphorylation of c-Jun by CSK, in opposition to c-Jun NH(2)-terminal kinase 1 and extracellular signal-regulated protein kinases, promoted c-Jun degradation and reduced stability. By promoting c-Jun degradation, CSK helps to maintain a low steady-state level of c-Jun, thereby inhibiting activator protein-1 activity and cell transformation caused by c-Jun. These results indicated that this function of CSK controls cell proliferation under normal growth conditions and may have implications for CSK loss of function in carcinogenesis.
authors.affiliation: Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Bu Young
authors.initials: BY
authors.lastname: Choi
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Ma
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Hong Seok
authors.initials: HS
authors.lastname: Choi
authors.forename: Akira
authors.initials: A
authors.lastname: Imamoto
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D025801:Ubiquitin; D019061:src-Family Kinases; D048055:Mitogen-Activated Protein Kinase 8