Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide

Shinobu, Noriaki; Iwamura, Tomokatsu; Yoneyama, Mitsutoshi; Yamaguchi, Kazumi; Suhara, Wakako; Fukuhara, Yukiko; Amano, Fumio; Fujita, Takashi

doi:10.1016/s0014-5793(02)02636-4

Cited by 44 publications

(34 citation statements)

References 24 publications

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“…Although 293 cells require ectopic expression of TLR3 to respond to dsRNA (38), viral infection can abrogate the requirement of TLR3 to generate IRF-3 holocomplex, 2 suggesting that viral infection may activate multiple pathways and poly(I⅐C) partly mimics it. Although different signals are triggered by different inducers, the signal is integrated at downstream resulting in the formation of IRF-3 holocomplex (27,40). The activation of the holocomplex does not require de novo protein synthesis but is a result of multiple protein-protein interactions and specific phosphorylations, and possibly acetylation, enabling a rapid response from the detection of pathogens to the final specific gene activation through alteration of chromatin structure.…”

Section: Discussionmentioning

confidence: 99%

Direct Involvement of CREB-binding Protein/p300 in Sequence-specific DNA Binding of Virus-activated Interferon Regulatory Factor-3 Holocomplex

Suhara¹,

Yoneyama²,

Kitabayashi³

et al. 2002

Journal of Biological Chemistry

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Infections of bacteria and viruses induce host defense reactions known as innate responses including the activation of interferon regulatory factor-3 (IRF-3), critical for the activation of type I interferon system. Upon immediate early signals triggered by the infection, IRF-3 is phosphorylated and a homodimer results. The homodimer complexes with the coactivator CREB-binding protein (CBP)/p300 in the nucleus; thus, holocomplex of IRF-3 competent in DNA binding is generated. We showed CBP/p300 to be indispensable for the DNA binding activity of the holocomplex and to aid the binding through direct interaction with the DNA. We demonstrated that p300 binds with the IRF-3 homodimer via a Q-rich domain and that an intact histone acetyltransferase (HAT) domain is indispensable for the DNA binding of the holocomplex along with a CH3 domain, which connects the HAT and Q-rich domains. These results highlight a novel function of CBP/p300: direct involvement in sequence-specific DNA binding. Furthermore, the critical function of these domains in virus-induced gene activation was demonstrated in vivo by using p300 mutants.

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Section: Discussionmentioning

confidence: 99%

Direct Involvement of CREB-binding Protein/p300 in Sequence-specific DNA Binding of Virus-activated Interferon Regulatory Factor-3 Holocomplex

Suhara¹,

Yoneyama²,

Kitabayashi³

et al. 2002

Journal of Biological Chemistry

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“…(20,21). IRF-3 activation upon LPS stimulation has also been demonstrated in Gal4-IRF-3 transactivation studies and in nuclear translocation assays (41,42). How LPS triggers these events is still not known.…”

Section: Tlr4 Stimulates Interaction Between P65 and Irf-3 At The Isrmentioning

confidence: 92%

Interferon Regulatory Factor-3-mediated Activation of the Interferon-sensitive Response Element by Toll-like receptor (TLR) 4 but Not TLR3 Requires the p65 Subunit of NF-κ

Wietek

Miggin

Jefferies

et al. 2003

Journal of Biological Chemistry

104

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Interferon regulatory factor (IRF) 3 is a transcription factor that binds the interferon-sensitive response element (ISRE) and is activated by Toll-like receptor 3 (TLR3) and TLR4. We have found that a dominant negative form of IB kinase 2 and a mutant form of IB, which acts as a super-repressor of NF-B, blocked activation of the ISRE by the TLR4 ligand lipopolysaccharide but not the TLR3 ligand poly(I-C). TLR4 failed to activate the ISRE in mouse embryonic fibroblasts bearing a targeted deletion of p65, whereas the response to TLR3 in these cells was normal. The p65 subunit of NF-B was detected in the lipopolysaccharide-activated but not poly(I-C)-activated ISRE-binding complex. Finally, p65 promoted transactivation of gene expression by IRF-3. These results therefore indicate that IRF-3-mediated activation of the ISRE by TLR4 but not TLR3 requires the p65 subunit of NF-B.

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“…These findings indicate that TRIF associates with TLR3 through the TIR domain and mediates the induction of IFN-␤ in response to poly(I:C). poly(I:C) and LPS stimulation has been shown to activate IRF-3 (6,19,20). Therefore, we next examined association of TRIF and IRF-3 (Fig.…”

Section: Trif Associates With Tlr3 and Irf-3mentioning

confidence: 99%

Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling

Yamamoto

Sato

Mori

et al. 2002

The Journal of Immunology

1,120

838

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MyD88 is a Toll/IL-1 receptor (TIR) domain-containing adapter common to signaling pathways via Toll-like receptor (TLR) family. However, accumulating evidence demonstrates the existence of a MyD88-independent pathway, which may explain unique biological responses of individual TLRs, particularly TLR3 and TLR4. TIR domain-containing adapter protein (TIRAP)/MyD88 adapter-like, a second adapter harboring the TIR domain, is essential for MyD88-dependent TLR2 and TLR4 signaling pathways, but not for MyD88-independent pathways. Here, we identified a novel TIR domain-containing molecule, named TIR domain-containing adapter inducing IFN-β (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-κB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-κB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-β promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-κB-dependent and IFN-β promoters. TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway.

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Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory factor 3 by lipopolysaccharide

Cited by 44 publications

References 24 publications

Direct Involvement of CREB-binding Protein/p300 in Sequence-specific DNA Binding of Virus-activated Interferon Regulatory Factor-3 Holocomplex

Direct Involvement of CREB-binding Protein/p300 in Sequence-specific DNA Binding of Virus-activated Interferon Regulatory Factor-3 Holocomplex

Interferon Regulatory Factor-3-mediated Activation of the Interferon-sensitive Response Element by Toll-like receptor (TLR) 4 but Not TLR3 Requires the p65 Subunit of NF-κ

Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling

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