Journal article
Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase recruitment
P Geserick, M Hupe, M Moulin, WWL Wong, M Feoktistova, B Kellert, H Gollnick, J Silke, M Leverkus
Journal of Cell Biology | ROCKEFELLER UNIV PRESS | Published : 2009
Abstract
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 CD..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
M. Moulin received a fellowship from the Association pour la Recherche sur le Cancer. J. Silke is supported by National Health and Medical Research Council grants 433013, 356256, 461221, 541901, and 541902. M. Leverkus is supported by grants of the Wilhelm-Sander-Stiftung (2008.072.1), Deutsche Krebshilfe (106849), Deutsche Forschungsgemeinschaft (Le 953/5-1 and Graduiertenkolleg 1167, TP6.1), Exzellenzfrderung (N2/C2; TP6) of Sachsen Anhalt, and the Berliner Stiftung fur Dermatologie. J. Silke is a consultant for TetraLogic Corp., and M. Leverkus has received an unrestricted research grant from TetraLogic Corp.