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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.
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340 news items

 
Nature.com
Fri, 19 Sep 2014 05:09:58 -0700

... best known as TRIF).181, 182, 183, 184 In the absence of RIPK1, TLR agonists and type I interferons trigger necroptosis even in caspase-competent cells,182, 183 suggesting that RIPK1 can inhibit necroptotic RCD as induced by these stimuli at two ...
 
St. Cloud Times
Sun, 14 Sep 2014 10:20:24 -0700

But Trif Lambos, who was down from Winnipeg to watch the game wearing face paint and his Peterson jersey, said he remains in the running back's corner — at least for now. "I don't know the whole story yet," Lambos said. "But until I hear more, I'm ...
 
Canadian Occupational Safety
Sun, 14 Sep 2014 16:15:00 -0700

Don't ever believe the company's TRIF rate: A lot of things are manipulated in life. The way in which a Total Recordable Injury Frequency (TRIF) rate is calculated can be a creative process. However, to voice a concern or note irregularities in the ...
 
Reuters
Mon, 15 Sep 2014 21:18:45 -0700

Sep 16 (Reuters) - Below are the ratings awarded by Investment Information Credit Rating Agency Ltd. (ICRA) for local debt instruments as of September 15, 2014. COMPANY INSTRUMENT RATING AMOUNT MOVEMENT (RS.
 
Rock Hill Herald (press release)
Wed, 03 Sep 2014 05:00:00 -0700

... L. Hayardeny, G.R. John; [P718] Laquinimod treatment prevents cuprizone-induced demyelination independent of Toll-like receptor signaling via MyD88 and TRIF (Poster Session 2, September 12, 2014, 14:45-16:15) N. Kramann, L. Menken, L. Hayardeny, ...

Glamour (blog)

Glamour (blog)
Wed, 27 Aug 2014 08:24:52 -0700

Mrs. Di cheated on her husband, Spencer's dad cheated with Mrs. Di, and the two had an illegitimate child, Aria's dad cheated on her mom, and Spence made out with two of Melissa's boyfriends. Trif. Ling. Mo and Spence manage to sneak out of Radley.
 
Seeking Alpha (registration)
Thu, 21 Aug 2014 15:18:45 -0700

And very pleasing to see a very significant improvement in our safety performance where our TRIF is down to 5 from 6.5 in the prior year. So overall, profits down a bit; we can explain why that's happening. Cash flow, very, very strong. And obviously ...
 
Sydney Morning Herald
Wed, 20 Aug 2014 04:46:54 -0700

I got Trif (Glen Trifiro) and Matty Sim from the NPL last season and they are no longer State League players - they are fully fledged A-League players. "I thought the Wolves played really well as a team, fought for each other and they were really hard ...
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