期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 1, 页码 442-454出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.413922
关键词
-
资金
- Slovenian Research Agency
- International Centre for Genetic Engineering and Biotechnology (CRP-ICGEB Research Grant Project) [CRP/SLO08-01]
- EN-FIST Centre of Excellence.
Translocation of nucleic acid-sensing (NAS) Toll-like receptors (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 because it regulates their response through trafficking to endosomes. We observed that poly(I: C) up-regulates transcription of UNC93B1 and promotes trafficking of TLR3 to the plasma membrane in human epithelial cell line. Up-regulation 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 up-regulation of UNC93B1. Our findings identified TLR3 as the important regulator of UNC93B1 that in turn governs the responsiveness of all NAS TLRs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据