COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation.
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.
Zhu
Feng
F
Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Choi
Bu Young
BY
Ma
Wei-Ya
WY
Zhao
Zhongliang
Z
Zhang
Yiguo
Y
Cho
Yong Yeon
YY
Choi
Hong Seok
HS
Imamoto
Akira
A
Bode
Ann M
AM
Dong
Zigang
Z
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*
D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D025801:Ubiquitin; D019061:src-Family Kinases; D048055:Mitogen-Activated Protein Kinase 8