Publication
Title
TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members
Author
Abstract
TNF receptor 1 signaling induces NF-kappa B 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-kappa B activation in L929 cells, therefore questioning the relative cytoprotective contribution of RIP1 ubiquitination versus canonical NF-kappa B activation. We found that attenuated NF-kappa B 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. Cell Death and Disease (2011) 2, e230; doi:10.1038/cddis.2011.111; published online 17 November 2011
Language
English
Source (journal)
Cell Death and Disease. - -
Publication
2011
ISSN
2041-4889
Volume/pages
2 (2011) , p. 1-10
Article Reference
e230
ISI
000297688600008
Medium
E-only publicatie
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 18.10.2018
Last edited 28.08.2021