Hepatitis B virus X protein increases the IL-1ß-induced NF-κB activation via interaction with evolutionarily conserved signaling intermediate in Toll pathways (ECSIT).
Virus Res
; 195: 236-45, 2015 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-25449573
ABSTRACT
Hepatitis B virus X protein (HBx) transactivates multiple transcription factors including nuclear factor-kappa B (NF-κB) that regulates inflammatory-related genes. However, the regulatory mechanism of HBx in NF-κB activation remains largely unknown. This study reports that HBx augments the interleukin-1ß (IL-1ß)-induced NF-κB activation via interaction with a Toll-like receptor (TLR) adapter protein, ECSIT (evolutionarily conserved signaling intermediate in Toll pathways). GST pull-down and co-immunoprecipitation analyses showed that HBx interacted with ECSIT. Deletion analysis of HBx in a CytoTrap two-hybrid system revealed that the interaction region of HBx for ECSIT was attributed to aa 51-80. Co-transfection of HBx and ECSIT in IL-1ß-stimulated cells appeared to activate IKK and IκB signaling pathway as phosphorylation of both IKK α/ß and IκBα was increased whereas knockdown of ECSIT or HBxΔ51-80 mutant attenuated the phosphorylation. As a consequence of IκBα degradation, NF-κB was activated as evidenced by increases in NF-κB transcriptional activity and the nuclear translocation of p65 and p50 that resulted in the induction of IL-10. In contrast, knockdown of ECSIT by siRNA or treatment with an NF-κB selective inhibitor (helenalin) abolished the NF-κB activation and IL-10 expression. We conclude that ECSIT appears to be a novel HBx-interacting signal molecule and their interaction is mechanistically important in IL-1ß induction of NF-κB activation.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Transativadores
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Vírus da Hepatite B
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NF-kappa B
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Proteínas Adaptadoras de Transdução de Sinal
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Interleucina-1beta
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Interações Hospedeiro-Patógeno
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article