Che-1 activates XIAP expression in response to DNA damage
| Autor: | M G Di Certo, M. Di Padova, F De Nicola, Agata Desantis, Simona Iezzi, M Scarsella, Carlo Leonetti, Claudio Passananti, Tommaso Bruno, Aristide Floridi, Maurizio Fanciulli |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Transcriptional Activation DNA damage Mice Nude X-Linked Inhibitor of Apoptosis Protein Biology Inhibitor of apoptosis Mice XIAP Transcription (biology) Cell Line Tumor Animals Humans Molecular Biology Checkpoint Kinase 2 Kinase NF-kappa B apoptosis Cell Biology Up-Regulation Antiapoptotic Agent Repressor Proteins Drug Resistance Neoplasm Che-1 Cancer research NIH 3T3 Cells Phosphorylation RNA Interference Apoptosis Regulatory Proteins Transcription Factors |
| Zdroj: | Cell death and differentiation 15 (2008): 515–520. doi:10.1038/sj.cdd.4402284 info:cnr-pdr/source/autori:T Bruno; S Iezzi; F De Nicola; M Di Padova; A Desantis; M Scarsella; M G Di Certo; C Leonetti; A Floridi; C Passananti; M Fanciulli/titolo:Che-1 activates XIAP expression in response to DNA damage/doi:10.1038%2Fsj.cdd.4402284/rivista:Cell death and differentiation/anno:2008/pagina_da:515/pagina_a:520/intervallo_pagine:515–520/volume:15 |
| DOI: | 10.1038/sj.cdd.4402284 |
| Popis: | 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-kappaB. 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. |
| Databáze: | OpenAIRE |
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