Dual specificity phosphatase 1/CL100 is a direct transcriptional target of E2F-1 in the apoptotic response to oxidative stress.
Dual specificity phosphatase 1/CL100 is a direct transcriptional target of E2F-1 in the apoptotic response to oxidative stress.
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DOI：
10.1158/0008-5472.can-06-4402
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发表时间：
2007-07
期刊：
影响因子：
11.2
通讯作者：
Jianli Wang;David Yin;Yu-Xin Liu;R. Baer;Yuxin Yin
中科院分区：
文献类型：
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作者：
Jianli Wang;David Yin;Yu-Xin Liu;R. Baer;Yuxin Yin
E2F-1 mediates apoptosis through transcriptional regulation of its targets. We report here that E2F-1 acts as a direct transcriptional regulator of dual specificity phosphatase 1 (DUSP1; CL100), a threonine and tyrosine phosphatase that inhibits mitogen-activated protein (MAP) kinases. We found that DUSP1 is transcriptionally induced by ectopic E2F-1 expression and that extracellular signal-regulated kinase 1/2 are dephosphorylated in the presence of E2F-1 and DUSP1. E2F-1 mediates apoptosis in the cellular response to oxidative stress. DUSP1 levels are significantly increased in an E2F-1-dependent manner following oxidative stress but not other stresses examined. DUSP1 mediates the cellular response to oxidative stress. We found that E2F-1 binds to chromatin encompassing the DUSP1 promoter and greatly stimulates the promoter activity of the DUSP1 gene. In particular, E2F-1 physically binds to an E2F-1 consensus sequence and a palindromic motif in the DUSP1 promoter. Interestingly, E2F-1 is acetylated following oxidative stress. Our findings show that E2F-1 is a transcriptional activator of DUSP1 and that DUSP1 is a link between E2F-1 and MAP kinases.
