Disease relevance of TICAM1

• These molecular motifs are encountered during viral and bacterial infection, and the apoptosis that occurs when TRIF is engaged represents an important host defense to limit the spread of infection [1].
• Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF [2].
• Although systemic parasitemia was comparable, sequestration of parasite and hemozoin load in the brain blood vessels was significantly lower in MyD88-deficient mice compared with those in TRIF-deficient or WT mice [3].

High impact information on TICAM1

• A critical component of the innate immune system, TLRs utilize leucine-rich-repeat motifs for ligand binding and a shared cytoplasmic domain to recruit the adaptors MyD88, TRIF, TIRAP, and/or TRAM for downstream signaling [4].
• Little is known about how TRIF pathway-dependent gene expression is regulated [5].
• SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production [5].
• Activating functions have been assigned to four TIR adaptors: MyD88, Mal, TRIF and TRAM [6].
• The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling [6].

Biological context of TICAM1

• Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif [1].
• Upon overexpression, TRIF was the sole TIR-adapter to potently engage mammalian cell death signaling pathways [1].
• Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways [7].
• In spite of the presence of a STAT1 (signal transduction and activators of transcription 1) motif at position -330, the addition of type I or type II interferon had no effect on TRIF activity [8].
• Here, we discuss how Trif and type I IFN are involved in the optimization of APC-T cell interaction in response not only to viral but also bacterial stimuli [9].

Anatomical context of TICAM1

• The addition of CyP together with LPS completely inhibited both MyD88- and TRIF-dependent pathways and suppressed the whole LPS-induced gene transcription program in human dendritic cells (DCs) [10].
• The activation of GEFH1-RhoB through the TRIF-dependent pathway of LPS in DC might be a critical target for controlling the activation of CD4+ T cells [11].
• Although dsRNA upregulated the expression of IFNbeta, LPS did not indicating that the TRIF-dependent branch of TLR4 signaling is inactive in astrocytes [12].
• This is in contrast to macrophages, which respond to LPS via both Trif- and MyD88-dependent pathways [13].
• We hypothesize that unlike antigen-presenting cells, vascular endothelial cells (ECs) lack the Trif protein TRAM and are therefore incapable of eliciting Trif-dependent immune responses to LPS [13].

Associations of TICAM1 with chemical compounds

• In LPS-mediated TLR4 activation, a complex of TICAM-1 and an additional TLR4-binding adapter serves as the adapter [14].
• Thus, a polyproline II interaction with the 3(10) helix likely facilitates NS3/4A recognition of TRIF, indicating a significant difference from NS3/4A recognition of viral substrates [15].
• HCV evasion of double-stranded RNA signaling through Toll-like receptor 3 is mediated by the viral protease NS3/4A, which directs proteolysis of its proline-rich adaptor protein, Toll-IL-1 receptor domain containing adaptor-inducing interferon-beta (TRIF) [15].
• These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling [16].
• To the Editor: role of MyD88 and Trif in acute allograft rejection: Glass half full or empty [17]?

Physical interactions of TICAM1

• Moreover, A20 interacted with TRIF in co-immunoprecipitation experiments [18].
• Finally, in co-immunoprecipitation experiments, we showed that PI3K physically interacted with TRIF [19].

Regulatory relationships of TICAM1

• Thus, the ability of TRIF to induce apoptosis was not dependent on its ability to activate either IFN regulatory factor-3 or NF-kappa B but was dependent on the presence of an intact RHIM [1].
• Expression of SARM blocked gene induction 'downstream' of TRIF but not of MyD88 [6].
• PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis [20].
• In addition, TRIF also induced apoptosis through a RIP/FADD/caspase-8-dependent and mitochondrion-independent pathway [7].
• The cleaved N-terminal but not C-terminal fragment of TRAF1 was responsible for inhibiting TRIF signaling [21].

Other interactions of TICAM1

• Zebrafish TICAM1 activates zebrafish IFN; however, it does so in an apparently IFN regulatory factor 3/7-independent manner [22].
• As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-kappaB-dependent promoter [23].
• These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway [23].
• We named this TLR4-TICAM-1-bridging adapter TICAM-2 [14].
• Here we characterize a fifth TIR adaptor, SARM, as a negative regulator of TRIF-dependent Toll-like receptor signaling [6].

Analytical, diagnostic and therapeutic context of TICAM1

• Circular dichroism (CD) spectroscopy confirmed that a substantial fraction of TRIF exists as polyproline II helices, and inclusion of the polyproline track increased affinity of P side TRIF peptides for the HCV-BK protease [15].
• After analysis of the nucleotide base sequences of a 1.2-kb fragment amplified from a dermatophyte fungus Trichophyton rubrum by arbitrarily primed PCR with random primer OPD18, a pair of primers (TRIF and TR1R) was designed and evaluated for specific identification of T. rubrum [24].

References