Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation.
Cell Rep
; 27(4): 1165-1175.e5, 2019 04 23.
Article
en En
| MEDLINE
| ID: mdl-31018131
ABSTRACT
Stimulator of interferon genes (STING) is a key regulator of type I interferon and pro-inflammatory responses during infection, cellular stress, and cancer. Here, we reveal a mechanism for how STING balances activation of IRF3- and NF-κB-dependent transcription and discover that acquisition of discrete signaling modules in the vertebrate STING C-terminal tail (CTT) shapes downstream immunity. As a defining example, we identify a motif appended to the CTT of zebrafish STING that inverts the typical vertebrate signaling response and results in dramatic NF-κB activation and weak IRF3-interferon signaling. We determine a co-crystal structure that explains how this CTT sequence recruits TRAF6 as a new binding partner and demonstrate that the minimal motif is sufficient to reprogram human STING and immune activation in macrophage cells. Together, our results define the STING CTT as a linear signaling hub that can acquire modular motifs to readily adapt downstream immunity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interferón Tipo I
/
FN-kappa B
/
Factor 6 Asociado a Receptor de TNF
/
Factor 3 Regulador del Interferón
/
Inmunidad Innata
/
Macrófagos
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos