ALG2 regulates type I interferon responses by inhibiting STING trafficking.
J Cell Sci
; 134(24)2021 12 15.
Article
em En
| MEDLINE
| ID: mdl-34787301
ABSTRACT
Stimulator of IFN genes (STING), an endoplasmic reticulum (ER) signaling adaptor, is essential for the type I interferon response to cytosolic double-stranded DNA. Translocation from the ER to perinuclear vesicles following cyclic GMP-AMP (cGAMP) binding is a critical step for STING to activate downstream signaling molecules, which leads to the production of interferon and pro-inflammatory cytokines. Here, we found that apoptosis-linked gene 2 (ALG2, also known as PDCD6) suppressed STING signaling induced by herpes simplex virus-1 (HSV-1) infection or cGAMP presence. Knockout of ALG2 markedly increased the expression of type I interferons upon cGAMP treatment or HSV-1 infection in THP-1 monocytes. Mechanistically, ALG2 associated with the C-terminal tail of STING and inhibited its trafficking from the ER to the perinuclear region. Furthermore, the ability of ALG2 to coordinate Ca2+ was crucial for its regulation of STING trafficking and DNA-induced innate immune responses. This work suggests that ALG2 is involved in DNA-induced innate immune responses by regulating STING trafficking.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
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Herpesvirus Humano 1
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Herpes Simples
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article