000170198 001__ 170198
000170198 005__ 20260407115449.0
000170198 0247_ $$2doi$$a10.1038/s41556-026-01886-z
000170198 0248_ $$2sideral$$a148703
000170198 037__ $$aART-2026-148703
000170198 041__ $$aeng
000170198 100__ $$aBetrancourt, Alexis
000170198 245__ $$aLysine-11 ubiquitination drives type-I/III interferon induction by cGAS–STING and Toll-like receptors 3 and 4
000170198 260__ $$c2026
000170198 5060_ $$aAccess copy available to the general public$$fUnrestricted
000170198 5203_ $$aPattern recognition receptor (PRR)-induced interferon (IFN) is critical for effective immunity. The PRRs Toll-like receptor (TLR) 3, TLR4 and cyclic GMP–AMP synthase (cGAS), together with the stimulator of IFN genes (STING), signal through TANK-binding kinase 1 (TBK1), which activates the type-I/III IFN-inducing transcription factor interferon-response factor 3 (IRF3). The mechanism by which these PRRs activate TBK1 remains unresolved. Here we show that lysine-11 (K11)-linked ubiquitination drives TBK1 activation by these PRRs. The E3 ligase ANKIB1 attaches K11-linked ubiquitin chains to components of the TLR3- and cGAS–STING-induced signalosomes. This facilitates Optineurin recruitment to these complexes, in turn enabling recruitment and activation of TBK1 and IRF3, defining an uncharacterized signalling axis. In mice, ANKIB1 deficiency dampens IFN induction via TLR3 and cGAS–STING, reducing interferonopathy and compromising protection against HSV-1, respectively. Together, our results demonstrate an unanticipated and critical role for ANKIB1-generated K11-linked ubiquitination in the immune response activated by cGAS–STING, TLR3 and TLR4.
000170198 536__ $$9info:eu-repo/grantAgreement/ES/MCIU-AEI/PID2020-113963RB-I00 Desasignar
000170198 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000170198 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000170198 700__ $$aCinko, M. Talha
000170198 700__ $$aVaranda, Ana Beatriz
000170198 700__ $$0(orcid)0000-0002-9730-2210$$aArias, Maykel$$uUniversidad de Zaragoza
000170198 700__ $$aUranga-Murillo, Iratxe
000170198 700__ $$aPeña, Natacha$$uUniversidad de Zaragoza
000170198 700__ $$aKaps, Lucia-Maria
000170198 700__ $$aChau, Long Fung
000170198 700__ $$aBuratti, Bianca
000170198 700__ $$aBrägelmann, Johannes
000170198 700__ $$ade Miguel, Diego
000170198 700__ $$aBecker, Kerstin
000170198 700__ $$aCasper, Ramona
000170198 700__ $$aMartin, Rocio
000170198 700__ $$aAlcami, Antonio
000170198 700__ $$aFerguson, Brian J.
000170198 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julian$$uUniversidad de Zaragoza
000170198 700__ $$aRieser, Eva
000170198 700__ $$aWalczak, Henning
000170198 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000170198 7102_ $$11013$$2830$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Traumatología y Ortopedia
000170198 773__ $$g28, 3 (2026), 608-621$$pNat. cell biol.$$tNATURE CELL BIOLOGY$$x1465-7392
000170198 8564_ $$s8753344$$uhttps://zaguan.unizar.es/record/170198/files/texto_completo.pdf$$yVersión publicada
000170198 8564_ $$s2461759$$uhttps://zaguan.unizar.es/record/170198/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000170198 909CO $$ooai:zaguan.unizar.es:170198$$particulos$$pdriver
000170198 951__ $$a2026-03-26-14:31:32
000170198 980__ $$aARTICLE