Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

C. C. Huang, J. M. Wang, U. Kikkawa, H. Mukai, M. R. Shen, I. Morita, B. K. Chen, W. C. Chang

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23 引文 斯高帕斯(Scopus)


The proto-oncogene c-Jun plays an important role in regulating tumor progression. We previously reported that the serine/threonine phosphatase calcineurin (CaN, also called PP2B) dephosphorylates the C-terminus (Ser-243) of c-Jun, resulting in the increase in c-Jun and Sp1 interaction, and subsequent c-Jun-induced gene expression. Here, we demonstrate the interaction of c-Jun and CaN in the nucleus of living cells by fluorescence resonance energy transfer assay and that this interaction is mediated through the calmodulin-binding domain of CaN. Furthermore, c-Jun protein stability was altered by CaN-mediated dephosphorylation at the Ser-243 site of c-Jun. The half-life of the c-Jun mutant, c-Jun-S243A was longer than that of the wild-type c-Jun. Moreover, silencing of endogenous CaN expression led to increased c-Jun ubiquitination and decreased stability. In 46% of clinical cervical tissue samples obtained from patients with cervical cancer, enhanced c-Jun and CaN expression, as well as decreased phospho-Ser-243 expression levels were detected. Our results suggest that CaN stabilizes c-Jun by dephosphorylating c-Jun at Ser-243 to enhance its tumorigenic ability.

頁(從 - 到)2422-2429
出版狀態已發佈 - 四月 10 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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