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

Open access
Vanlangenakker, N, Bertrand, M J M, Bogaert, P, Vandenabeele, P, Vanden Berghe, T·2011·Cell Death & Disease

Abstract

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.

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Metadata

Authors
Vanlangenakker, N., Bertrand, M. J. M., Bogaert, P., Vandenabeele, P., & Vanden Berghe, T.
Venue
Cell Death & Disease
Published
2011-11-17
Volume
2
Issue
11
Pages
e230-e230
ISSN
2041-4889 (ISSN-L)
OpenAlex
W1976647852
Cited by
233
References
12
FWCI
7.05
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. https://app.cochat.ai/papers/10.1038/cddis.2011.111
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Vanlangenakker, N., Bertrand, M. J. M., Bogaert, P., Vandenabeele, P., & Vanden Berghe, T. (2011). TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death & Disease. https://doi.org/10.1038/cddis.2011.111

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