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TY - JOUR AU - Huang, C-C AU - Wang, J-M AU - Kikkawa, U. AU - Mukai, H. AU - Shen, M-R AU - Morita, I. AU - Chen, B-K AU - Chang, W-C PY - 2008 DA - 2008/04/01 TI - Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation JO - Oncogene SP - 2422 EP - 2429 VL - 27 IS - 17 AB - 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. SN - 1476-5594 UR - https://doi.org/10.1038/sj.onc.1210888 DO - 10.1038/sj.onc.1210888 ID - Huang2008 ER -