CIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation

ABSTRACT: Cellular inhibitor of apoptosis proteins (cIAPs) are RING-containing E3 ubiquitin ligases that ubiquitylate receptor-interacting protein kinase 1 (RIPK1) to regulate TNF signalling. Here, we established mice simultaneously expressing enzymatically-inactive cIAP1/2 variants, bearing mutations in the RING domains of cIAP1/2 (cIAP1/2 mutant RING, cIAP1/2MutR). cIap1/2MutR/MutR mice died during embryonic development due to RIPK1-mediated apoptosis. While expression of kinase-inactive RIPK1D138N rescued embryonic development, Ripk1D138N/D138N/cIap1/2MutR/MutR mice developed systemic inflammation and died post-weaning. Cells expressing cIAP1/2MutR and RIPK1D138N were still susceptible to TNF-induced apoptosis and necroptosis, implying additional kinase-independent RIPK1 activities in regulating

SUBMITTER: Dr. Fabian Schorn 

PROVIDER: S-SCDT-10_15252-EMBJ_2023113614 | biostudies-other |

REPOSITORIES: biostudies-other