Che-1 activates XIAP expression in response to DNA damage

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)515-520
Number of pages6
JournalCell Death and Differentiation
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 2008

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bruno, T., Iezzi, S., De Nicola, F., Di Padova, M., Desantis, A., Scarsella, M., Di Certo, M. G., Leonetti, C., Floridi, A., Passananti, C., & Fanciulli, M. (2008). Che-1 activates XIAP expression in response to DNA damage. Cell Death and Differentiation, 15(3), 515-520. https://doi.org/10.1038/sj.cdd.4402284