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, cIAP1/2^MutR ). cIap1/2^MutR/MutR mice died during embryonic development due to RIPK1-mediated apoptosis. While expression of kinase-inactive RIPK1^D138N rescued embryonic development, Ripk1^D138N/D138N /cIap1/2^MutR/MutR mice developed systemic inflammation and died postweaning. Cells expressing cIAP1/2^MutR and RIPK1^D138N were still susceptible to TNF-induced apoptosis and necro

SUBMITTER: Schorn F 

PROVIDER: S-EPMC10646551 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature