Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5.
J Exp Med
; 214(4): 973-989, 2017 04 03.
Article
em En
| MEDLINE
| ID: mdl-28250012
ABSTRACT
Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells. Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection. At the late phase of viral infection, both MDA5 and RIG-I are desumoylated by SENP2, resulting in their K48-linked polyubiquitination and degradation. These findings suggest that dynamic sumoylation and desumoylation of MDA5 and RIG-I modulate efficient innate immunity to RNA virus and its timely termination.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus de RNA
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Sumoilação
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Proteína DEAD-box 58
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Helicase IFIH1 Induzida por Interferon
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China