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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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Sat, 25 Oct 2014 00:01:41 -0700

Former Romanian football agent Robert Cristian Trif could become the first foreign owner of a football club in the United Arab Emirates (UAE). Trif, 35, has asked the country's football federation for permission to register his team, Athletic Dubai, in ...


Tue, 21 Oct 2014 05:43:33 -0700

În aproximativ 3 săptămâni, Trif va afla dacă echipa sa, Dubai Athletic, va face parte din eşalonul secund al campionatului din Emirate, acolo unde au rămas trei locuri goale, după dizolvarea cluburilor Al Raams, Al Jazira Al Hamra şi Al Arabi ...


Mon, 20 Oct 2014 07:05:54 -0700

Athletic Dubai will play in blue and white with a falcon emblem and Trif claims they have the option of three unnamed Dubai stadiums to call home. Ilie Balaci, the Romanian former coach of Al Shabab, Al Ahli and Al Ain, is also thought to be a ...
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Thu, 23 Oct 2014 08:10:47 -0700

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Wed, 15 Oct 2014 06:03:36 -0700

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Tue, 30 Sep 2014 13:43:54 -0700

The airport will be able to begin funding a new Terminal Renewal and Improvement Fund (TRIF) with deposits up to $125 million per year. To date, $25.4 million has been deposited and over time this account will enhance LAX's ability to support internal ...
Tue, 21 Oct 2014 05:11:15 -0700

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Tue, 21 Oct 2014 12:03:19 -0700

Hunedoreanul Robert Cristian Trif (foto, dreapta), 35 de ani, aflat de 14 ani în Dubai, devenind unul dintre cei mai importanţi impresari din Asia, ar putea fi primul proprietar străin al unui club din Emirate. Aşteaptă doar ca noua grupare, Athletic ...

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