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FEBS Lett. 2015 Jul 8;589(15):1819-24. doi: 10.1016/j.febslet.2015.05.028. Epub 2015 May 27.

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

Author information

1
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia; Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia. Electronic address: laman.al@yandex.ru.
2
Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia; Pieta Research, Edinburgh EH10 5YW, UK. Electronic address: rlathe@pieta-research.org.
3
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
4
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia; Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia.
5
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
6
Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia; Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Little France, Edinburgh EH16 4TJ, UK; Skolkovo Institute of Science and Technology, Moscow Region, Russia.
7
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.

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.

KEYWORDS:

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

PMID:
26026270
DOI:
10.1016/j.febslet.2015.05.028
[Indexed for MEDLINE]
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