Wagner, Klaus, Engels, Ingo and Deveraux, Quinn (2004) Caspase-2 can function upstream of bid cleavage in the TRAIL apoptosis pathway. The Journal of Biological Chemistry, 279 (33). pp. 35047-35052. ISSN 0021-9258

Abstract

In many mammalian cell types, engagement of the TRAIL/Apo2L death receptors DR4 and DR5 alters mitochondrial physiology, thereby promoting the release of pro-apoptotic proteins normally contained within this organelle. A contemporary view of this process is that in so-called type II cells death receptor-activated caspase-8 cleaves the Bcl-2 family member Bid, which generates a truncated Bid fragment that collaborates with Bax, another Bcl-2 relative, to promote the release of mitochondrial factors necessary for activation of executioner caspases and apoptosis. Here we show that in some type II cells caspase-2 is necessary for optimal TRAIL-mediated cleavage of Bid. Down-regulation of caspase-2 using RNA interference significantly inhibited TRAIL-induced apoptosis. Analysis of the TRAIL proteolytic cascade following gene silencing of specific pathway components revealed that caspase-2 is necessary for efficient cleavage of Bid; however, caspase-2 proteolytic processing, which occurs downstream of Bax, is not necessary for its role in Bid cleavage.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1074/jbc.M400708200
Additional Information:	free final full text version available at publisher's official URL; author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1074/jbc.M400708200
Date Deposited:	14 Dec 2009 14:02
Last Modified:	31 Jan 2013 01:21
URI:	https://oak.novartis.com/id/eprint/273