Innate immunity: Bacterial cell-wall muramyl peptide targets the conserved transcription factor YB-1

• Published in: FEBS letters 2015-07, Vol.589 (15), p.1819-1824
• Main Authors: Laman, A.G., Lathe, R., Savinov, G.V., Shepelyakovskaya, A.O., Boziev, Kh.M., Baidakova, L.K., Chulin, A.N., Brovko, F.A., Svirshchevskaya, E.V., Kotelevtsev, Y., Eliseeva, I.A., Guryanov, S.G., Lyabin, D.N., Ovchinnikov, L.P., Ivanov, V.T.
• Format: Article
• Language: English
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - analogs & derivatives; Acetylmuramyl-Alanyl-Isoglutamine - metabolism; Animals; Bacteria; Bacteria - metabolism; Base Sequence; Binding Sites; Cell Wall - metabolism; Cells, Cultured; DNA Primers; Glucosaminyl-muramyl dipeptide; Immunity, Innate; Innate immunity; Mice; Muramyl peptide; Y-box protein 1; Y-Box-Binding Protein 1 - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.05.028

•Bacterial cell wall glucosaminyl-muramyl dipeptide (GMDP) binds to multifunctional factor YB-1.•GMDP and YB-1 demonstrate subcellular co-localization.•GMDP and YB-1 co-induce NF-κB2 transcription, cleavage and transport to the nucleus.•GMDP and YB-1 co-induce chemokine production. The bacterial cell wall muramyl dipeptides MDP and glucosaminyl-MDP (GMDP) are powerful immunostimulators but their binding target remains controversial. We previously reported expression cloning of GMDP-binding polypeptides and identification of Y-box protein 1 (YB-1) as their sole target. Here we show specific binding of GMDP to recombinant YB-1 protein and subcellular colocalization of YB-1 and GMDP. GMDP binding to YB-1 upregulated gene expression levels of NF-κB2, a mediator of innate immunity. Furthermore, YB-1 knockdown abolished GMDP-induced Nfkb2 expression. GMDP/YB-1 stimulation led to NF-κB2 cleavage, transport of activated NF-κB2 p52 to the nucleus, and upregulation of NF-κB2-dependent chemokine Cxcr4 gene expression. Therefore, our findings identify YB-1 as new target for muramyl peptide signaling.