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STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NF-kB signaling


ABSTRACT: STING activation by cyclic dinucleotides in mammals induces IRF3- and NF-kB -mediated gene expression in mammals, as well as lipidation of LC3B at Golgi-related membranes. While mechanisms of the IRF3 response are well understood, the mechanisms of NF-kB activation via STING remain unclear. We report that STING activation induces linear/M1-linked ubiquitin chain (M1-Ub) formation and recruitment of the LUBAC E3 ligase, HOIP, to LC3B-associated Golgi membranes where ubiquitin is also localized. Loss of HOIP prevents formation of M1-Ub ubiquitin chains and reduces STING-induced NF-kB and IRF3 signaling in human THP1 monocytes and mouse bone marrow-derived macrophages, without affecting STING activation. STING-induced LC3B lipidation is not required for M1-Ub chain formation or for immune-related gene expression, but the recently reported STING function in neutralizing Golgi pH may be involved. Thus, LUBAC synthesis of M1-linked ubiquitin chains mediates STING-induced innate-immune signaling.

SUBMITTER: Dr. Tara, D Fischer 

PROVIDER: S-SCDT-10_1038-S44318-024-00291-2 | biostudies-other |

REPOSITORIES: biostudies-other

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