STING induces LUBAC-mediated synthesis of linear ubiquitin chains to stimulate innate immune signaling.
bioRxiv
; 2023 Oct 16.
Article
em En
| MEDLINE
| ID: mdl-37873486
ABSTRACT
STING activation by cyclic dinucleotides in mammals induces interferon- and NFκB -related gene expression, and the lipidation of LC3B at Golgi membranes. While mechanisms of the interferon response are well understood, the mechanisms of NFκB activation mediated by STING remain unclear. We report that STING activation induces K63- and M1-linked/linear ubiquitin chain formation at LC3B-associated Golgi membranes. Loss of the LUBAC E3 ubiquitin ligase prevents formation of linear, but not K63-linked ubiquitin chains or STING activation and inhibits STING-induced NFκB and IRF3-mediated signaling in monocytic THP1 cells. The proton channel activity of STING is also important for both K63 and linear ubiquitin chain formation, and NFκB- and interferon-related gene expression. Thus, LUBAC synthesis of linear ubiquitin chains regulates STING-mediated innate immune signaling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos