LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation.
EMBO J
; 37(3): 351-366, 2018 02 01.
Article
en En
| MEDLINE
| ID: mdl-29288164
ABSTRACT
The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy. Depletion of either LRRC25 or ISG15 abrogates RIG-I-p62 interaction as well as the autophagic degradation of RIG-I. Collectively, our findings identify a previously unrecognized role of LRRC25 in type I IFN signaling activation by which LRRC25 acts as a secondary receptor to assist RIG-I delivery to autophagosomes for degradation in a p62-dependent manner.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
/
Interferón Tipo I
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Proteínas de Unión al ARN
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Proteína 58 DEAD Box
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Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article