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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-58098

Geserick, P; Hupe, M; Moulin, M; Wong, W. Wei-Lynn; Feoktistova, M; Kellert, B; Gollnick, H; Silke, J; Leverkus, M (2009). cIAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment. Journal of Cell Biology, 187(7):1037-1054.

Published Version (English)


A role for cellular inhibitors of apoptosis (IAPs [cIAPs])
in preventing CD95 death has been suspected but
not previously explained mechanistically. In this
study, we find that the loss of cIAPs leads to a dramatic
sensitization to CD95 ligand (CD95L) killing. Surprisingly,
this form of cell death can only be blocked by a combination
of RIP1 (receptor-interacting protein 1) kinase and caspase
inhibitors. Consistently, we detect a large increase in
RIP1 levels in the CD95 death-inducing signaling complex
(DISC) and in a secondary cytoplasmic complex (complex II)
in the presence of IAP antagonists and loss of RIP1-
protected cells from CD95L/IAP antagonist–induced death.
Cells resistant to CD95L/IAP antagonist treatment could
be sensitized by short hairpin RNA–mediated knockdown
of cellular FLICE-inhibitory protein (cFLIP). However, only
cFLIPL and not cFLIPS interfered with RIP1 recruitment to the
DISC and complex II and protected cells from death. These
results demonstrate a fundamental role for RIP1 in CD95
signaling and provide support for a physiological role of
caspase-independent death receptor–mediated cell death.



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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:15 Jun 2012 15:23
Last Modified:03 Dec 2012 20:49
Publisher:Rockefeller University Press

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