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

A. G. Laman*, R. Lathe, G. V. Savinov, A. O. Shepelyakovskaya, Kh M. Boziev, L. K. Baidakova, A. N. Chulin, F. A. Brovko, E. V. Svirshchevskaya, Y. Kotelevtsev, I. A. Eliseeva, S. G. Guryanov, D. N. Lyabin, L. P. Ovchinnikov, V. T. Ivanov

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract 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.

Original languageEnglish
Article number37184
Pages (from-to)1819-1824
Number of pages6
JournalFEBS Letters
Volume589
Issue number15
DOIs
Publication statusPublished - 3 Jul 2015

Keywords

  • Glucosaminyl-muramyl dipeptide
  • Innate immunity
  • Muramyl peptide
  • Y-box protein 1

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