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  • The role of UNC93B1 protein in surface localization of TLR3 receptor and in cell priming to nucleic acid agonists [Elektronski vir]
    Pohar, Jelka, 1984- ...
    Translocation of nucleic acid sensing Toll-like receptors (NAS TLRs) to endosomes is essential for response to microbial nucleic acids as well as for prevention of the autoimmune response. The ... accessory protein UNC93B1 is indispensable for activation of NAS TLRs since it regulates their response through trafficking to endosomes. We observed that poly(I:C) upregulates transcription of UNC93B1 and promotes trafficking of TLR3 to the plasma membrane in human epithelial cell line. Upregulation of UNC93B1 is triggered through TLR3 activation by poly(I:C). Further studies revealed that expression of UNC93B1 promotes trafficking of differentially glycosylated TLR3, but not other NAS TLRs, to the plasma membrane. UNC93B1 promoter region contains binding sites for poly(I:C)- and type I interferon-inducible regulatory elements. UNC93B1 also increases the protein lifetime of TLR3 and TLR9 and augments signaling of all NAS TLRs. Furthermore, we discovered that poly(I:C) pretreatment primes B-cells to the activation by ssDNA via upregulation of UNC93B1. Our findings identified TLR3 as the important regulator of UNC93B1 that in turn governs the responsiveness of all NAS TLRs.
    Source: Journal of biological chemistry [Elektronski vir]. - ISSN 1083-351X (Vol. 288, iss. 1, 4 Jan. 2013, str. 442-454)
    Type of material - e-article ; adult, serious
    Publish date - 2013
    Language - english
    COBISS.SI-ID - 5143066