DUSP6 is a novel transcriptional target of p53 and regulates p53-mediated apoptosis by modulating expression levels of Bcl-2 family proteins

作者：Piya Sujan; Kim Ji Young; Bae Jeehyeon; Seol Dai Wu; Moona Ae Ran; Kim Tae Hyoung^*

来源：FEBS Letters, 2012, 586(23): 4233-4240.

DOI：10.1016/j.febslet.2012.10.031

• p53
• DUSP6
• ERK
• Bcl-2 family protein
• Cell death

p53 regulates various cellular responses through transcriptional regulation of distinct sets of target genes. Dual specificity phosphatase 6 (DUSP6) is a cytosolic phosphatase that inactivates the extracellular-signal-regulated kinase 1/2 (ERK1/2). This study demonstrates that p53 transactivates DUSP6 in human colorectal HCT116 cells to regulate ERK1/2 in p53-mediated cell death. DUSP6 is transactivated by p53 overexpression and genotoxic agents, and chromatin immunoprecipitation revealed two p53-binding sites in the DUSP6 promoter responsible for DUSP6 induction. Expression of shDUSP6 inhibited 5%26apos;-FU-induced cell death, whereas overexpression of DUSP6 increased susceptibility to 5%26apos;-FU. 5%26apos;-FU treatment dephosphorylated ERK in a DUSP6-dependent manner, resulting in destabilization of Bcl-2 and stabilization of Bad. These results provide insights on the modulatory role of p53 in the survival pathway by up-regulating DUSP6.

• 出版日期2012-11-30