TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members

TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members

TNF receptor 1 signaling induces NF-κB activation and necroptosis in L929 cells. We previously reported that cellular inhibitor of apoptosis protein-mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1-deubiqui...

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Main Authors: Vanlangenakker, N, Bertrand, M J M, Bogaert, P, Vandenabeele, P, Vanden Berghe, T
Format: Online
Language:English
Published: Nature Publishing Group 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223695/
id pubmed-3223695
recordtype oai_dc
spelling pubmed-32236952011-12-15 TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members Vanlangenakker, N Bertrand, M J M Bogaert, P Vandenabeele, P Vanden Berghe, T Original Article TNF receptor 1 signaling induces NF-κB activation and necroptosis in L929 cells. We previously reported that cellular inhibitor of apoptosis protein-mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1-deubiquitinating enzyme, protects against tumor necrosis factor (TNF)-induced necroptosis. We report here that RIP1 is a crucial mediator of canonical NF-κB activation in L929 cells, therefore questioning the relative cytoprotective contribution of RIP1 ubiquitination versus canonical NF-κB activation. We found that attenuated NF-κB activation has no impact on TNF-induced necroptosis. However, we identified A20 and linear ubiquitin chain assembly complex as negative regulators of necroptosis. Unexpectedly, and in contrast to RIP3, we also found that knockdown of RIP1 did not block TNF cytotoxicity. Cell death typing revealed that RIP1-depleted cells switch from necroptotic to apoptotic death, indicating that RIP1 can also suppress apoptosis in L929 cells. Inversely, we observed that Fas-associated protein via a death domain, cellular FLICE inhibitory protein and caspase-8, which are all involved in the initiation of apoptosis, counteract necroptosis induction. Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions. Nature Publishing Group 2011-11 2011-11-17 /pmc/articles/PMC3223695/ /pubmed/22089168 http://dx.doi.org/10.1038/cddis.2011.111 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Vanlangenakker, N
Bertrand, M J M
Bogaert, P
Vandenabeele, P
Vanden Berghe, T
spellingShingle Vanlangenakker, N
Bertrand, M J M
Bogaert, P
Vandenabeele, P
Vanden Berghe, T
TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
author_facet Vanlangenakker, N
Bertrand, M J M
Bogaert, P
Vandenabeele, P
Vanden Berghe, T
author_sort Vanlangenakker, N
title TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
title_short TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
title_full TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
title_fullStr TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
title_full_unstemmed TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
title_sort tnf-induced necroptosis in l929 cells is tightly regulated by multiple tnfr1 complex i and ii members
description TNF receptor 1 signaling induces NF-κB activation and necroptosis in L929 cells. We previously reported that cellular inhibitor of apoptosis protein-mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1-deubiquitinating enzyme, protects against tumor necrosis factor (TNF)-induced necroptosis. We report here that RIP1 is a crucial mediator of canonical NF-κB activation in L929 cells, therefore questioning the relative cytoprotective contribution of RIP1 ubiquitination versus canonical NF-κB activation. We found that attenuated NF-κB activation has no impact on TNF-induced necroptosis. However, we identified A20 and linear ubiquitin chain assembly complex as negative regulators of necroptosis. Unexpectedly, and in contrast to RIP3, we also found that knockdown of RIP1 did not block TNF cytotoxicity. Cell death typing revealed that RIP1-depleted cells switch from necroptotic to apoptotic death, indicating that RIP1 can also suppress apoptosis in L929 cells. Inversely, we observed that Fas-associated protein via a death domain, cellular FLICE inhibitory protein and caspase-8, which are all involved in the initiation of apoptosis, counteract necroptosis induction. Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions.
publisher Nature Publishing Group
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223695/
_version_ 1611489871790080000

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