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2015 ; 16
(4
): 447-55
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WDFY1 mediates TLR3/4 signaling by recruiting TRIF
#MMPMID25736436
Hu YH
; Zhang Y
; Jiang LQ
; Wang S
; Lei CQ
; Sun MS
; Shu HB
; Liu Y
EMBO Rep
2015[Apr]; 16
(4
): 447-55
PMID25736436
show ga
Toll-like receptors (TLRs) are pattern recognition receptors that sense a variety
of pathogens, initiate innate immune responses, and direct adaptive immunity. All
TLRs except TLR3 recruit the adaptor MyD88 to ultimately elicit inflammatory gene
expression, whereas TLR3 and internalized TLR4 use TIR-domain-containing adaptor
TRIF for the induction of type I interferon and inflammatory cytokines. Here, we
identify the WD repeat and FYVE-domain-containing protein WDFY1 as a crucial
adaptor protein in the TLR3/4 signaling pathway. Overexpression of WDFY1
potentiates TLR3- and TLR4-mediated activation of NF-?B, interferon regulatory
factor 3 (IRF3), and production of type I interferons and inflammatory cytokines.
WDFY1 depletion has the opposite effect. WDFY1 interacts with TLR3 and TLR4 and
mediates the recruitment of TRIF to these receptors. Our findings suggest a
crucial role for WDFY1 in bridging the TLR-TRIF interaction, which is necessary
for TLR signaling.
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