The inhibitory effect of TNFAIP3 on NF-κB signaling is generated from the cooperative activity of its two ubiquitin-editing domains: the N-terminal ovarian tumor domain (OTU), responsible for deubiquitinating receptor interacting protein 1 (RIP1), an essential adaptor protein of the TNF-induced signaling pathway, and the C-terminal zinc finger-containing domain, which functions as an E3 ubiquitin ligase promoting the proteasomal degradation of RIP1 [17]. The gene discussed is RIPK1; the disease is ovarian neoplasm.