RNF8 negatively regulates NF-kappaB signaling by targeting IkappaB kinase: implications for the regulation of inflammation signaling.
Biochem Biophys Res Commun
; 488(1): 189-195, 2017 06 17.
Article
em En
| MEDLINE
| ID: mdl-28499869
ABSTRACT
Persistent or excess activation of NF-κB leads to cancer, autoimmune and inflammatory diseases. Therefore, activated NF-κB needs to be terminated after induction, which highlights the physiological significance of NF-κB-negative regulators. However, the molecular mechanisms that negatively regulate NF-κB are not well understood. Here, we report that Ring Finger Protein 8 (RNF8), an E3 ubiquitin ligase, inhibits TNFα-mediated NF-κB activation by targeting IκB kinase (IKK). Upon TNFα stimulation, RNF8 binds to the catalytic subunits of IKK complex, resulting in inhibition of IKKα/ß phosphorylation and subsequent NF-κB activation. RNF8 targets the IKK complex in a manner independent of its RING domain. We further provide evidence that the silencing of RNF8 results in enhanced TNFα-induced IKK activation, and an increase expression of NF-κB-induced inflammatory cytokine IL-8. Our study identifies a previously unrecognized role for RNF8 in the negative regulation of NF-κB activation by targeting and deactivating the IKK complex.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Regulação para Baixo
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NF-kappa B
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Proteínas de Ligação a DNA
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Quinase I-kappa B
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Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China