Cdc25A promotes cell survival by stimulating NF-魏B activity through I魏B-伪 phosphorylation and destabilization

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• 作者：Hey-Young Hong^a ; Jiyeon Choi^a ; Young-Wook Cho^b ; Byung-Chul Kim^a ; ^{bckim@kangwon.ac.kr}
• 关键词：Cdc25A ; NF-魏B ; I魏-B伪 ; Ubiquitination ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：6 April, 2012
• 卷：420
• 期：2
• 页码：293-296
• 文件大小：485 K

摘要

Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-魏B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I魏-B伪) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-魏B. Inhibition of NF-魏B activity by chemical inhibitor or overexpression of I魏-B伪 in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-魏B activity regulation and it may be an important survival mechanism of cancer cells.