Journal article
TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1.
DM Moujalled, WD Cook, T Okamoto, J Murphy, KE Lawlor, JE Vince, DL Vaux
Cell Death Disease | Published : 2013
Open access
Abstract
Ligation of tumor necrosis factor receptor 1 (TNFR1) can cause cell death by caspase 8 or receptor-interacting protein kinase 1 (RIPK1)- and RIPK3-dependent mechanisms. It has been assumed that because RIPK1 bears a death domain (DD), but RIPK3 does not, RIPK1 is necessary for recruitment of RIPK3 into signaling and death-inducing complexes. To test this assumption, we expressed elevated levels of RIPK3 in murine embryonic fibroblasts (MEFs) from wild-type (WT) and gene-deleted mice, and exposed them to TNF. Neither treatment with TNF nor overexpression of RIPK3 alone caused MEFs to die, but when levels of RIPK3 were increased, addition of TNF killed WT, Ripk1(-/-), caspase 8(-/-), and Bax(-..
View full abstractGrants
Awarded by National Science Foundation
Funding Acknowledgements
This work was funded by NHMRC grants and fellowships 433063, 461221, 541901, 575512, 637342, 1003435, and ARC fellowship FT100100100, and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. We thank Stephen Hedrick, Michelle Kelliher, and Heinrich Korner for caspase 8, TRADD, FADD, and RIPK1 gene-deleted cell lines and mice, and Mark McKinlay (TetraLogic Pharmaceuticals) for smac-mimetic compound. We would also like to acknowledge Ian Gentle for helping construct the 4HT-inducible FLAG RIPK3 construct.