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Che-1 activates XIAP expression in response to DNA damage.
- Source :
- Cell Death & Differentiation; Mar2008, Vol. 15 Issue 3, p515-520, 6p, 2 Black and White Photographs, 2 Graphs
- Publication Year :
- 2008
-
Abstract
- X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family that selectively binds and inhibits caspase-3, -7 and -9. As such, XIAP is an extremely potent suppressor of apoptosis and an attractive target for cancer treatment. Che-1 is an antiapoptotic agent involved in the control of gene transcription and cell proliferation. Recently, we showed that the checkpoint kinases ATM/ATR and checkpoint kinase 2 physically and functionally interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce transcription of p53, and Che-1 depletion strongly sensitizes tumor cells to anticancer drugs. Here we show that Che-1 activates XIAP expression in response to DNA damage. This effect is mediated by Che-1 phosphorylation and requires NF-κB. Notably, we found that XIAP expression is necessary for antiapoptotic activity of Che-1 and that in vivo downregulation of Che-1 by small interference RNA strongly enhanced the cytotoxicity of anticancer drugs.Cell Death and Differentiation (2008) 15, 515–520; doi:10.1038/sj.cdd.4402284; published online 30 November 2007 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 15
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 30000963
- Full Text :
- https://doi.org/10.1038/sj.cdd.4402284