Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery.
Sci Adv
; 6(24): eaba7589, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32582856
ABSTRACT
The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bioinspired method using TM-deficient STING may present a universally applicable platform for cGAMP delivery.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Nucleotídeos Cíclicos
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos