Cdc25A promotes cell survival by stimulating NF-{kappa}B activity through I{kappa}B-{alpha} phosphorylation and destabilization
- Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)
- Korea Basic Science Institute, Chuncheon Center, Gangwondaehak-gil 1, Chuncheon 200-701 (Korea, Republic of)
Highlights: Black-Right-Pointing-Pointer We examine the antiapoptotic mechanisms of Cdc25A. Black-Right-Pointing-Pointer Smad7 decreases the phosphorylation of I{kappa}B-alpha at Ser-32. Black-Right-Pointing-Pointer Smad7 positively regulates NF-{kappa}B activity through I{kappa}B-alpha ubiquitination. -- Abstract: 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-{kappa}B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I{kappa}-B{alpha}) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-{kappa}B. Inhibition of NF-{kappa}B activity by chemical inhibitor or overexpression of I{kappa}-B{alpha} 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-{kappa}B activity regulation and it may be an important survival mechanism of cancer cells.
- OSTI ID:
- 22207793
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 420, Issue 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
NF-{kappa}B signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells
Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway