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Title: cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms
Authors: Feoktistova, M.
Geserick, P.
Kellert, B.
Dimitrova, D. P.
Langlais, Claudia
Hupe, M.
Cain, K.
MacFarlane, Marion
Häcker, G.
Leverkus, M.
First Published: 5-Aug-2011
Publisher: Elsevier (Cell Press)
Citation: Molecular Cell, 2011, 43 (3), pp. 449-463
Abstract: The intracellular regulation of cell death pathways by cIAPs has been enigmatic. Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. This 2 MDa intracellular complex that we designate "Ripoptosome" is necessary but not sufficient for cell death. It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms. cFLIP(L) prevents Ripoptosome formation, whereas, intriguingly, cFLIP(S) promotes Ripoptosome assembly. When cIAPs are absent, caspase activity is the "rheostat" that is controlled by cFLIP isoforms in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis or caspase-dependent apoptosis. RIP1 is the core component of the complex. As exemplified by our studies for TLR3 activation, our data argue that the Ripoptosome critically influences the outcome of membrane-bound receptor triggering. The differential quality of cell death mediated by the Ripoptosome may cause important pathophysiological consequences during inflammatory responses.
DOI Link: 10.1016/j.molcel.2011.06.011
ISSN: 1097-2765
eISSN: 1097-4164
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2011 Elsevier Inc. Under a Creative Commons license ( ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, College of Medicine, Biological Sciences and Psychology

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