biostudies-literatureUnknown107(36)Arimoto KThe rapid induction of type I IFN is a central event of the innate defense against viral infections and is tightly regulated by a number of cellular molecules. Viral components induce strong type I IFN responses through the activation of toll-like receptors (TLRs) and intracellular cytoplasmic receptors such as an RNA helicase RIG-I and/or MDA5. According to recent studies, the NF-kappaB essential modulator (NEMO, also called IKKgamma) is crucial for this virus-induced antiviral response. However, the precise roles of signal activation by NEMO adaptor have not been elucidated. Here, we show that virus-induced IRF3 and NF-kappaB activation depends on the K(lys)-27-linked polyubiquitination to NEMO by the novel ubiquitin E3 ligase triparite motif protein 23 (TRIM23). Virus-induced IRF3 and NProceedings of the National Academy of Sciences of the United States of America15856-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC2936632biostudies-literaturePolyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense.PMC2936632Takeuchi OSaeki YMurakami YFunami KShimotohno KArimoto KAkira SOkawa KTanaka KfalsePolyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense.The rapid induction of type I IFN is a central event of the innate defense against viral infections and is tightly regulated by a number of cellular molecules. Viral components induce strong type I IFN responses through the activation of toll-like receptors (TLRs) and intracellular cytoplasmic receptors such as an RNA helicase RIG-I and/or MDA5. According to recent studies, the NF-kappaB essential modulator (NEMO, also called IKKgamma) is crucial for this virus-induced antiviral response. However, the precise roles of signal activation by NEMO adaptor have not been elucidated. Here, we show that virus-induced IRF3 and NF-kappaB activation depends on the K(lys)-27-linked polyubiquitination to NEMO by the novel ubiquitin E3 ligase triparite motif protein 23 (TRIM23). Virus-induced IRF3 and N2010-01-01T00:00:00Z2010 Sep2025-04-19T09:51:47.945Z2019-03-27T00:33:56ZS-EPMC29366322072466010.1073/pnas.1004621107