COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation

Feng Zhu, Bu Young Choi, Wei-Ya Ma, Zhongliang Zhao, Yiguo Zhang, Yong Yeon Cho, Hong Seok Choi, Akira Imamoto, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 NH2-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.

Original languageEnglish (US)
Pages (from-to)5729-5736
Number of pages8
JournalCancer Research
Volume66
Issue number11
DOIs
StatePublished - Jun 1 2006

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