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

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-kappa B2, a mediator of innate immunity. Furthermore, YB-1 knockdown abolished GMDP-induced Nfkb2 expression. GMDP/YB-1 stimulation led to NF-kappa B2 cleavage, transport of activated NF-kappa B2 p52 to the nucleus, and upregulation of NF-kappa B2-dependent chemoldne Cxcr4 gene expression. Therefore, our findings identify YB-1 as new target for muramyl peptide signaling. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.