Journal article

RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during development

Holly Anderton, Esther Bandala-Sanchez, Daniel S Simpson, James A Rickard, Ashley P Ng, Ladina Di Rago, Cathrine Hall, James E Vince, John Silke, Gianmaria Liccardi, Rebecca Feltham



RIPK1 is an essential downstream component of many pattern recognition and death receptors. RIPK1 can promote the activation of caspase-8 induced apoptosis and RIPK3-MLKL-mediated necroptosis, however, during development RIPK1 limits both forms of cell death. Accordingly, Ripk1-/- mice present with systemic cell death and consequent multi-organ inflammation, which is driven through the activation of both FADD-caspase-8 and RIPK3-MLKL signaling pathways causing perinatal lethality. TRADD is a death domain (DD) containing molecule that mediates signaling downstream of TNFR1 and the TLRs. Following the disassembly of the upstream receptor complexes either RIPK1 or TRADD can form a complex with ..

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Awarded by National Health and Medical Research Project

Awarded by Independent Research Institutes Infrastructure Support Scheme Grant

Awarded by NHMRC scholarship

Funding Acknowledgements

We thank Pascal Meier for his support and acknowledge that the idea underlying this study was presented and discussed during a Meier lab retreat, we thank the staff in the WEHI Bioservices facility and Histology Department. We thank Michelle Kelliher for the Ripk1<SUP>-/-</SUP> mice, Heinrich Korner for the Tnfr1<SUP>-/-</SUP> mice and Tak W. Mak for the Tradd<SUP>-/-</SUP> mice [29]. This work was supported by National Health and Medical Research Project grants (1081272, 1046984, 1057888, 1101405, 1060179), fellowships to J.E.V. (1052598) and J.S 1107149, Independent Research Institutes Infrastructure Support Scheme Grant (9000220), a Victorian State Government Operational Infrastructure Support Grant and an Australian Government Research Training Program Scholarship and NHMRC scholarship to H.A (1093637). G.L. was supported by the ICR Dean Award and by Breast Cancer Now.