Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44860
Title: Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival.
Authors: Horn, S
Hughes, MA
Schilling, R
Sticht, C
Tenev, T
Ploesser, M
Meier, P
Sprick, MR
MacFarlane, M
Leverkus, M
First Published: 25-Apr-2017
Publisher: Elsevier
Citation: Cell Reports, 19 (4), pp. 785-797
Abstract: Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.
DOI Link: 10.1016/j.celrep.2017.04.010
eISSN: 2211-1247
Links: http://hdl.handle.net/2381/44860
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The accession number for the microarray dataset reported in this paper is GEO: GSE75365. Supplementary information is available to download from the publisher's website at https://doi.org/10.1016/j.celrep.2017.04.010
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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