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toll-like receptor adaptor molecule 1
Symbol TICAM1
Alt. symbols TRIF
Entrez 148022
HUGO 18348
OMIM 607601
RefSeq NM_014261
UniProt Q8IUC6
Other data
Locus Chr. 19 p13.3

TIR-domain-containing adapter-inducing interferon-β (TRIF) is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.[1]

Toll-like receptors (TLRs) recognize specific components of microbial invaders and activate an immune response to these pathogens. After these receptors recognize highly-conserved pathogenic patterns, a downstream signaling cascade is activated in order to stimulate the release of inflammatory cytokines and chemokines as well as to upregulate the expression of immune cells. All TLRs have a TIR domain that initiates the signaling cascade through TIR adapters. Adapters are platforms that organize downstream signaling cascades leading to a specific cellular response after exposure to a given pathogen.[2]


TRIF is primarily active in the spleen and is often regulated when MyD88 is deficient in the liver, indicating organ-specific regulation of signaling pathways. Curiously, there is a lack of redundancy within the TLR4 signaling pathway that leads to microbial evasion of immune response in the host after mutations occur within intermediates of the pathway.[3] Three TRAF-binding motifs present in the amino terminal region of TRIF are necessary for association with TRAF6. Destruction of these motifs reduced the activation of NF-κβ, a transcription factor that is also activated by the carboxy-terminal domain of TRIF in the upregulation of cytokines and co-stimulatory immune molecules. This domain recruits receptor-interacting protein (RIP1) and RIP3 through the RIP homotypic interaction motif. Cells deficient for RIP1 gene display attenuated TLR3 activation of NF-κβ, indicating the use of the RIP1 gene in downstream TRIF activation, in contrast to other TLRs that use IRAK protein for the activation of NF-κβ.[4]

Areas of research[edit]

Investigations into the function of TRIF are of great significance to various fields of biomedical research. The pathogenesis of infectious disease, septic shock, tumor growth, and rheumatoid arthritis all have close ties with TLR signaling pathways, specifically to that of TRIF. Better understanding of the TRIF pathway will be therapeutically useful in the development of vaccines and treatments that can control associated inflammation and antiviral responses. Experiments involving wild-type and TRIF-deficient mice are critical for understanding the coordinated responses of TLR pathways. It is necessary to study the coordinated effects of these pathways in order to understand the complex responses initiated by TRIF.[5]


  1. ^ Palsson-McDermott, Eva and Luke A J O’Neill (2004) Immunology. 113(2) 153-162
  2. ^ Guo B, Cheng G (2007). "Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK". J. Biol. Chem. 282 (16): 11817–26. doi:10.1074/jbc.M700017200. PMID 17327220. 
  3. ^ Palsson-McDermott, Eva and Luke A J O’Neill (2004) Immunology. 113(2) 153-162
  4. ^ Kawai, Taro and Shizuo Akira. (2004). Arthritis Res. Ter. 7(1) 12-19
  5. ^ Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K (2007). "Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation". Biochem. Biophys. Res. Commun. 354 (4): 1045–51. doi:10.1016/j.bbrc.2007.01.090. PMID 17275788. 

External links[edit]

Original courtesy of Wikipedia: http://en.wikipedia.org/wiki/TRIF — Please support Wikipedia.
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De Paște, vedetele se întrec în preparate delicioase, cozonaci, fripturi de miel, drob și ouă cât mai colorate. Nu face rabat, nici folclorista Florina Trif, care a petrecut ore bune în bucutărie la plămăditul cozonacilor și la înroșitul ouălor. Și cum ...
Yahoo News Romania
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În zi de sărbătoare, salvatorii din Apuseni au aprins lumânări pentru cei pe care nu i-au putut salva din avionul prăbuşit pe 20 ianuarie. Moţii au petrecut prima zi de Paşte acasă, aşa cum cere tradiţia locului. Gheorghe Trif şi Argentin Todea, doi ...
7thSpace Interactive (press release)
Wed, 23 Apr 2014 00:41:15 -0700

Methods: Tlr4-, Myd88- and Trif-knockout animals, as well as C57BL/6 mice, were used for the wild type control. For the in vivo study, we used a mouse model of retinal IR injury. To test the role of protein kinase C (PKC) in IR injury, IR retinas were ...
Wed, 16 Apr 2014 21:14:48 -0700

Pepsin digest of wheat gliadin fraction increases production of IL-1beta via TLR4/MyD88/TRIF/MAPK/NF-kappaB signaling pathway and an NLRP3 inflammasome activation. PLoS One 2013; 8:e62426. Broughton SE, Petersen J, Theodossis A, et al. Biased T ...


Wed, 09 Apr 2014 11:16:03 -0700

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7thSpace Interactive (press release)
Fri, 28 Mar 2014 09:30:00 -0700

However, the correlation between TLR4/MyD88-dependent and TLR4/TRIF-dependent pathways in BSCB dysfunction is not fully understood. The aim of this study is to characterize inflammatory responses in spinal cord I/R and the events that define its ...
Marketwired (press release)
Fri, 04 Apr 2014 08:56:15 -0700

Industry measures its safety performance using a formula known as Total Recordable Incident Frequency (TRIF). TRIF for the rigs has seen significant improvement in the last decade. Incident frequency has been cut to one-third of what it was ten years ago.
Wed, 23 Apr 2014 09:52:30 -0700

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