title: Innate immunity: Bacterial cell-wall muramyl peptide targets the conserved transcription factor YB-1.
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.
authors.affiliation: 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.
authors.forename: A G
authors.initials: AG
authors.lastname: Laman
authors.affiliation: Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia; Pieta Research, Edinburgh EH10 5YW, UK. Electronic address: rlathe@pieta-research.org.
authors.forename: R
authors.initials: R
authors.lastname: Lathe
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: G V
authors.initials: GV
authors.lastname: Savinov
authors.affiliation: 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.
authors.forename: A O
authors.initials: AO
authors.lastname: Shepelyakovskaya
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: Kh M
authors.initials: KhM
authors.lastname: Boziev
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: L K
authors.initials: LK
authors.lastname: Baidakova
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: A N
authors.initials: AN
authors.lastname: Chulin
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: F A
authors.initials: FA
authors.lastname: Brovko
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Svirshchevskaya
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Kotelevtsev
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Eliseeva
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: S G
authors.initials: SG
authors.lastname: Guryanov
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: D N
authors.initials: DN
authors.lastname: Lyabin
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
authors.forename: L P
authors.initials: LP
authors.lastname: Ovchinnikov
authors.affiliation: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
authors.forename: V T
authors.initials: VT
authors.lastname: Ivanov
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D007113:Immunity, Innate; D051379:Mice; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D051840:Y-Box-Binding Protein 1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine
keywords: Glucosaminyl-muramyl dipeptide; Innate immunity; Muramyl peptide; Y-box protein 1