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toll-like receptor adaptor molecule 1
Identifiers
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]

Structure[edit]

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]

References[edit]

  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.
This page uses Creative Commons Licensed content from Wikipedia. A portion of the proceeds from advertising on Digplanet goes to supporting Wikipedia.

2264 news items

 
Science Magazine
Tue, 14 Jul 2015 12:06:29 -0700

Through a combination of mathematical modeling and single-cell imaging analysis, Cheng et al. found that whereas MyD88 was required for the initial peak of transient NF-κB activation in all LPS-stimulated cells, TRIF was required for more sustained NF ...

New Jersey Law Journal

New Jersey Law Journal
Tue, 07 Jul 2015 11:27:55 -0700

Chechelnitsky and Trif began dating, and around the same time, he told her that Modugno had authorized him to assign work to her, the suit claimed. Trif regularly bragged about his relationship with Modugno and told Chechelnitsky she would go far if ...
 
BMC Blogs Network
Fri, 24 Jul 2015 06:30:00 -0700

To date, a number of TLR signaling pathway mediators have been identified and studied in zebrafish such as the adaptor proteins Myd88, Tirap (Mal), Trif and Sarm1 [34]–[38], and the downstream signaling intermediates Irak and Traf6 [39], [40].

Above the Law

Above the Law
Tue, 07 Apr 2015 15:22:29 -0700

At the “after party” Associate Trif told Plaintiff that some attorneys were going to get sushi and that she should join them. When they arrived at the sushi restaurant, Associate Trif admitted to Plaintiff that no one else was joining them because he ...

ProSport

ProSport
Mon, 27 Jul 2015 04:03:45 -0700

Titus Trif a călătorit timp de 11 ore împreună cu mama sa pentru a fi alături de echipa favorită. Când au ajuns la Bucureşti, suporterii ardeleni au aflat că gazdele nu au pus în vânzare bilete pentru sectorul dedicat oaspeţilor. Fanii clujeni au găsit ...
 
Crain's Chicago Business
Tue, 06 Jan 2015 11:17:38 -0800

A trust affiliated with Trif purchased the complex for about $11.9 million in 2005, according to Cook County property records. Other than some mechanical maintenance, the seller had not done any major renovations on the three-building complex ...

Aradon

Aradon
Sat, 25 Jul 2015 00:47:57 -0700

... fost: Andrieș Cosmina, Bejan Oana, Brie Oana, Damian Alexandra, Groșan Giulia, Groza Roxana, Ioan Emanuela, Pasc Andra, Popovici Denisa, Poșta Florentina, Șușca Nicoleta, Bianca Tirsin, Toader Romina, Tomoiagă Sandra, Trif Simona, Troi Lorena ...
 
Baltimore Sun
Wed, 20 Mar 2013 12:25:30 -0700

"The Sun's journalism is thriving, and Trif Alatzas has been a driving force behind our success," Timothy E. Ryan, publisher, president and CEO of the Baltimore Sun Media Group, said in a statement. "He was especially instrumental in directing the ...
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