TRAF6-mediated degradation of DOK3 is required for production of IL-6 and TNFα in TLR9 signaling.
Mol Immunol
; 68(2 Pt C): 699-705, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26548852
ABSTRACT
Our previous study showed that the downstream of kinase 3 (DOK3) is degraded during macrophage stimulation with CpG. However, the underlying mechanism and role in Toll-like receptor 9 (TLR9) signaling remains elusive. In this study, we demonstrate that CpG treatment leads to ubiquitin-mediated degradation of DOK3 via interaction with an E3 ligase TNFR-associated factor 6 (TRAF6). We also identified the 27th amino acid (lysine) of DOK3 is responsible for Ly48 polyubiquitination of DOK3. Furthermore, reintroduction of DOK3 (K27R) into DOK3-deficient macrophages abolishes DOK3 degradation induced by CpG and suppresses the production of IL-6 and TNFα. More importantly, our study uncovers a novel role of an E3 ligase TRAF6, namely, TRAF6 is also able to catalyse Lys 48 polyubiquitylation of target protein except for Lys 63 polyubiquitylation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Interleucina-6
/
Fator de Necrose Tumoral alfa
/
Proteínas Adaptadoras de Transdução de Sinal
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Fator 6 Associado a Receptor de TNF
/
Receptor Toll-Like 9
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China