TICAM1

TICAM1 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.[7] Three TRAF-binding motifs present in the amino terminal region of TICAM1 are necessary for association with TRAF6. Destruction of these motifs reduced the activation of NF-κB, a transcription factor that is also activated by the carboxy-terminal domain of TICAM1 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-κB, indicating the use of the RIP1 gene in downstream TICAM1 activation, in contrast to other TLRs that use IRAK protein for the activation of NF-κB.[8]

Investigations into the function of TICAM1 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 TICAM1 . Better understanding of the TICAM1 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 TICAM1-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 TICAM1.[9]

• Toll-like receptor signaling pathway - Reference pathway (KO) from the KEGG website.
• TICAM1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)