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

Research output: Contribution to journalArticle

  • 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

Related Edinburgh Organisations

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

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.

    Research areas

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

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