Optineurin regulates the interferon response in a cell cycle-dependent manner.
PLoS Pathog
; 11(4): e1004877, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25923723
ABSTRACT
Viral invasion into a host is initially recognized by the innate immune system, mainly through activation of the intracellular cytosolic signaling pathway and coordinated activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB) transcription factors that promote type I interferon gene induction. The TANK-binding Kinase 1 (TBK1) phosphorylates and activates IRF3. Here, we show that Optineurin (Optn) dampens the antiviral innate immune response by targeting the deubiquitinating enzyme CYLD to TBK1 in order to inhibit its enzymatic activity. Importantly, we found that this regulatory mechanism is abolished at the G2/M phase as a consequence of the nuclear translocation of CYLD and Optn. As a result, we observed, at this cell division stage, an increased activity and phosphorylation of TBK1 that lead to its relocalization to mitochondria and to enhanced interferon production, suggesting that this process, which relies on Optn function, might be of major importance to mount a preventive antiviral response during mitosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Interferon beta
/
Proteínas Serina-Treonina Quinases
/
Proteínas Supressoras de Tumor
/
Fator de Transcrição TFIIIA
/
Imunidade Inata
/
Mitose
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article