摘要
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.
原文 | 英語 |
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頁(從 - 到) | 2422-2429 |
頁數 | 8 |
期刊 | Oncogene |
卷 | 27 |
發行號 | 17 |
DOIs | |
出版狀態 | 已發佈 - 4月 10 2008 |
ASJC Scopus subject areas
- 分子生物學
- 遺傳學
- 癌症研究