Cactin targets the MHC class III protein IkappaB-like (IkappaBL) and inhibits NF-kappaB and interferon-regulatory factor signaling pathways.
J Biol Chem
; 285(47): 36804-17, 2010 Nov 19.
Article
em En
| MEDLINE
| ID: mdl-20829348
ABSTRACT
Toll-like receptors (TLRs) act as primary sensors of the immune system by recognizing specific microbial motifs and inducing proinflammatory genes that facilitate innate and adaptive immunity. TLRs regulate gene expression by activating transcription factors, such as NF-κB and interferon-regulatory factors. Dysregulation of these pathways can lead to inflammatory diseases, and thus they are subject to stringent control by negative regulators of innate immune signaling. Cactin (Cactus interactor) was initially discovered as a novel interactor of Drosophila Cactus, a regulator of Drosophila Toll signaling. We now describe the first functional characterization of the human ortholog of Cactin (hCactin) and show that it acts as a negative regulator of TLRs. Overexpression of hCactin suppresses TLR-induced activation of NF-κB and interferon-regulatory factor transcription factors and induction of TLR-responsive genes, whereas knockdown of endogenous hCactin augments TLR induction of these responses. hCactin also interacts with IκB-like protein and targets other proteins that are encoded by genes in the MHC Class III region of chromosome 6. We demonstrate that hCactin localizes to the nucleus, and this nuclear localization is critical for manifesting its inhibitory effects on TLR signaling. This study thus defines hCactin as a novel negative regulator of TLR signaling and reveals its capacity to target MHC Class III genes at the molecular and functional level.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas de Transporte
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NF-kappa B
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Proteínas I-kappa B
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Proteínas de Drosophila
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Fatores Reguladores de Interferon
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Receptores Toll-Like
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Complexo Principal de Histocompatibilidade
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2010
Tipo de documento:
Article