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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAaA9PzEp5rmSWN04wh5ByESwKyCayh64bNJJWsC44Oqc#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAaA9PzEp5rmSWN04wh5ByESwKyCayh64bNJJWsC44Oqc#_3 http://www.w3.org/ns/prov#value In contrast to Bid, the antiapoptotic members of the Bcl-2 protein family, such as Bcl-2 and Bcl-xL, are known to preserve the integrity of the mitochondrial membrane (34). We thus explored whether the Siva-induced apoptosis in T cells could be modulated by overexpression of Bcl-2 or Bcl-xL. Jurkat T cells overexpressing either Bcl-2 or Bcl-xL were transiently transfected with the GFP-Siva-1 expression vector, and cell surface PS exposure was analyzed 48 h later on GFP-positive cells (Fig. 5C). Expression of GFP-Siva-1 in control Jurkat cells stably transfected with the neomycin vector resulted in an apoptotic level absolutely similar to that observed in HPB-ALL T cells. In contrast, the percentage of GFP-Siva-1-expressing cells displaying a cell surface exposure of PS was reduced to a level corresponding to the GFP control in cells coexpressing Bcl-2 or Bcl-xL. These results show that the proapoptotic activity of GFP-Siva-1 in Jurkat T cells can be totally abrogated by overexpression of either Bcl-2 or Bcl-xL antiapoptotic proteins. Because studies on the Fas-mediated apoptosis signaling pathways have highlighted two types of cells (35) depending on the requirement (type II cells such as Jurkat cells) or not (type I cells) of a mitochondrial amplification loop, we explored the Siva-induced apoptosis in a type I cell line such as SKW6.4 B lymphoid cells overexpressing Bcl-2 (35). In contrast to Jurkat cells, overexpression of Bcl-2 in SKW6.4 cells only reduced by 50% the proportion of apoptotic GFP-Siva-1-expressing cells (Fig. 5D). This result indicates that the Siva-induced apoptosis is also, at least in part, modulated by antiapoptotic members of the Bcl-2 protein family in type I cells. 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