title: The Role of the Phylogenetically Conserved Cochaperone Protein Droj2/DNAJA3 in NF-κB Signaling.
abstract: The NF-κB pathway is a phylogenetically conserved signaling pathway with a central role in inflammatory and immune responses. Here we demonstrate that a cochaperone protein, Droj2/DNAJA3, is involved in the activation of canonical NF-κB signaling in flies and in human cultured cells. Overexpression of Droj2 induced the expression of an antimicrobial peptide in Drosophila. Conversely, Droj2 knockdown resulted in reduced expression of antimicrobial peptides and higher susceptibility to Gram-negative bacterial infection in flies. Similarly, Toll-like receptor-stimulated IκB phosphorylation and NF-κB activation were suppressed by DNAJA3 knockdown in HEK293 cells. IκB kinase overexpression-induced NF-κB phosphorylation was also compromised in DNAJA3 knockdown cells. Our study reveals a novel conserved regulator of the NF-κB pathway acting at the level of IκB phosphorylation.
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Momiuchi
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kumada
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan, PRESTO Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Tokyo 332-0012, Japan, and.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuraishi
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takagaki
authors.affiliation: the Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Oshima
authors.affiliation: From the Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan, kurata@m.tohoku.ac.jp.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kurata
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D010802:Phylogeny; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; C120664:DNAJA3 protein, human; D029721:Drosophila Proteins; D050956:HSP40 Heat-Shock Proteins; D016328:NF-kappa B; D051550:I-kappa B Kinase
keywords: Drosophila; NF-κB; inflammation; innate immunity; signaling