Journal article
IAPs limit activation of RIP kinases by TNF receptor 1 during development
M Moulin, H Anderton, AK Voss, T Thomas, WWL Wong, A Bankovacki, R Feltham, D Chau, WD Cook, J Silke, DL Vaux
EMBO Journal | Published : 2012
Abstract
Inhibitor of apoptosis (IAP) proteins cIAP1, cIAP2, and XIAP (X-linked IAP) regulate apoptosis and cytokine receptor signalling, but their overlapping functions make it difficult to distinguish their individual roles. To do so, we deleted the genes for IAPs separately and in combination. While lack of any one of the IAPs produced no overt phenotype in mice, deletion of cIap1 with cIap2 or Xiap resulted in mid-embryonic lethality. In contrast, Xiap -/-cIap2-/- mice were viable. The death of cIap2 -/-cIap1-/- double mutants was rescued to birth by deletion of tumour necrosis factor (TNF) receptor 1, but not TNFR2 genes. Remarkably, hemizygosity for receptor-interacting protein kinase 1 (Ripk1)..
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Awarded by Japan Society for the Promotion of Science
Funding Acknowledgements
This work was funded by a Centre grant from the Leukemia and Lymphoma Society, and NHMRC grants and fellowships 433063, 461221, 541901, 575512, 1003435, and was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. We thank Michelle Kelliher for providing Ripk1<SUP>+/-</SUP> mice; Vishva Dixit for the Ripk3<SUP>-/-</SUP> mice; Heinrich Korner for the Tnfr1<SUP>-/-</SUP> and Tnfr2<SUP>-/-</SUP> mice; Mark McKinlay for biotinylated and non-biotinylated Smac mimetic compounds (TetraLogic Pharmaceuticals). We thank CAH staff at Latrobe University, especially Jose Ramos, Samantha Kelly, and Melinda Boulton for mouse husbandry, and Frank Koentgen (Ozgene) for generating the cIap2<SUP>FRT/FRT</SUP>cIap1<SUP>lox/lox</SUP> mice.