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

Nele Vanlangenakker (UGent) , Mathieu Bertrand (UGent) , Pieter Bogaert (UGent) , Peter Vandenabeele (UGent) and Tom Vanden Berghe (UGent)
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
RIP1, TNF-induced necroptosis, A20, LUBAC, TUMOR-NECROSIS-FACTOR, NF-KAPPA-B, DEATH DOMAIN KINASE, SIGNALING COMPLEX, INDUCED APOPTOSIS, FACTOR RECEPTOR-1, ACTIVATION, ALPHA, RIP1, UBIQUITINATION

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Citation

Please use this url to cite or link to this publication:

Chicago
Vanlangenakker, Nele, Mathieu Bertrand, Pieter Bogaert, Peter Vandenabeele, and Tom Vanden Berghe. 2011. “TNF-induced Necroptosis in L929 Cells Is Tightly Regulated by Multiple TNFR1 Complex I and II Members.” Cell Death & Disease 2.
APA
Vanlangenakker, N., Bertrand, 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, 2.
Vancouver
1.
Vanlangenakker N, Bertrand 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. CELL DEATH & DISEASE. 2011;2.
MLA
Vanlangenakker, Nele, Mathieu Bertrand, Pieter Bogaert, et al. “TNF-induced Necroptosis in L929 Cells Is Tightly Regulated by Multiple TNFR1 Complex I and II Members.” CELL DEATH & DISEASE 2 (2011): n. pag. Print.
@article{1996578,
  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.},
  articleno    = {e230},
  author       = {Vanlangenakker, Nele and Bertrand, Mathieu and Bogaert, Pieter and Vandenabeele, Peter and Vanden Berghe, Tom},
  issn         = {2041-4889},
  journal      = {CELL DEATH \& DISEASE},
  keyword      = {RIP1,TNF-induced necroptosis,A20,LUBAC,TUMOR-NECROSIS-FACTOR,NF-KAPPA-B,DEATH DOMAIN KINASE,SIGNALING COMPLEX,INDUCED APOPTOSIS,FACTOR RECEPTOR-1,ACTIVATION,ALPHA,RIP1,UBIQUITINATION},
  language     = {eng},
  pages        = {10},
  title        = {TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members},
  url          = {http://dx.doi.org/10.1038/cddis.2011.111},
  volume       = {2},
  year         = {2011},
}

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