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Sci. STKE, 27 August 2002
Vol. 2002, Issue 147, p. tw320
[DOI: 10.1126/stke.2002.147.tw320]

EDITORS' CHOICE

Apoptosis First Things First

Cells responding to cytotoxic stresses like DNA damage are thought to activate apoptosis-inducing caspases only after the mitochondria are permeabilized and release their cytochrome c, which functions as a caspase activator. Lassus et al. (see the Perspective by Kumar and Vaux) present experimental results challenging this view. They monitored apoptosis caused by DNA damage in human fibroblasts transformed with the adenoviral oncogene E1A and in other human tumor cell lines. When small interfering RNA (siRNA) was used to block expression of caspase-2, release of proapoptotic factors from the mitochondria was inhibited and the percentage of cells undergoing apoptosis was reduced. Apoptosis was restored by the expression of mutant caspase-2 RNA that was designed not to interact with siRNA (see the Protocol by Lassus et al.). Thus, even "intrinsic" death-inducing pathways activated by DNA damage include caspase activation as an early event in order to permeabilize the mitochondria.

P. Lassus, X. Opitz-Araya, Y. Lazebnik, Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization, Science 297, 1352-1354 (2002). [Abstract] [Full Text]

S. Kumar, D. L. Vaux, A Cinderella caspase takes center stage, Science 297, 1290-1291 (2002). [Summary] [Full Text]

P. Lassus, J. Rodriguez, Y. Lazebnik, Confirming specificity of RNAi in mammalian cells, Science's STKE (2002), http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2002/147/pl13 [Abstract] [Full Text]

Citation: First Things First. Sci. STKE 2002, tw320 (2002).



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