IRTKS negatively regulates antiviral immunity through PCBP2 sumoylation-mediated MAVS degradation.
Nat Commun
; 6: 8132, 2015 Sep 08.
Article
in En
| MEDLINE
| ID: mdl-26348439
ABSTRACT
RNA virus infection is recognized by the RIG-I family of receptors that activate the mitochondrial adaptor MAVS, leading to the clearance of viruses. Antiviral signalling activation requires strict modulation to avoid damage to the host from exacerbated inflammation. Insulin receptor tyrosine kinase substrate (IRTKS) participates in actin bundling and insulin signalling and its deficiency causes insulin resistance. However, whether IRTKS is involved in the regulation of innate immunity remains elusive. Here we show that IRTKS deficiency causes enhanced innate immune responses against RNA viruses. IRTKS-mediated suppression of antiviral responses depends on the RIG-I-MAVS signalling pathway. IRTKS recruits the E2 ligase Ubc9 to sumoylate PCBP2 in the nucleus, which causes its cytoplasmic translocation during viral infection. The sumoylated PCBP2 associates with MAVS to initiate its degradation, leading to downregulation of antiviral responses. Thus, IRTKS functions as a negative modulator of excessive inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA-Binding Proteins
/
Vesiculovirus
/
Rhabdoviridae Infections
/
Ubiquitin-Conjugating Enzymes
/
Adaptor Proteins, Signal Transducing
/
Immunity, Innate
/
Macrophages
/
Microfilament Proteins
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2015
Document type:
Article
Affiliation country: