TBK1-associated protein in endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways.
J Biol Chem
; 286(9): 7043-51, 2011 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-21189260
ABSTRACT
The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways. We found that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-ß and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-ß induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-ß. TAPE knockdown failed to block Trif-mediated IFN-ß induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-ß induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas de Ligação a DNA
/
Receptor 3 Toll-Like
/
Receptor 4 Toll-Like
/
Fatores Imunológicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article