Este articulo nos habla de un nuevo participante en la respuesta apoptotica al daño al ADN, como en la quimioterapia, funcionando rio arriba de la expresion de las IAPs, que a su vez son reguladas por NFkB. Esto nos provee de nuevas preguntas en nuestro tema
Che-1 activates XIAP expression in response to DNA damage Cell Death and Differentiation advance online publication 30 November 2007; doi: 10.1038/sj.cdd.4402284
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-
B. 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.
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