title: p100, a precursor of NF-κB2, inhibits c-Rel and reduces the expression of IL-23 in dendritic cells.
abstract: Nuclear factor κB regulates various genes involved in the immune response, inflammation, cell survival, and development. NF-κB activation is controlled by proteins possessing ankyrin repeats, such as IκBs. A precursor of the NF-κB2 (p52) subunit, p100, contains ankyrin repeats in its C-terminal portion and has been found to act as a cytoplasmic inhibitor of RelA in the canonical pathway of NF-κB activation. Here, we demonstrate that p100 also suppresses c-Rel function in dendritic cells. Expression of the p19 and p40 subunits of IL-23, a c-Rel-dependent cytokine, was enhanced in p100-deficient cells, although expression of a RelA-dependent cytokine, TNF-α, was reduced. Nuclear translocation of c-Rel was enhanced in p100-deficient cells. p100, and not the processed p52 form, associated with c-Rel in the steady state and dissociated immediately after lipopolysaccharide stimulation in wild-type dendritic cells. Four hours after the stimulation, p100 was newly synthesized and associated with c-Rel again. In cells expressing both c-Rel and RelA, c-Rel is preferentially suppressed by p100.
authors.affiliation: Technology and Development Team for BioSignal Program, Subteam for BioSignal Integration, RIKEN BioResource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba 305-0074, Japan. Electronic address: smise@brc.riken.jp.
authors.forename: Setsuko
authors.initials: S
authors.lastname: Mise-Omata
authors.affiliation: Technology and Development Team for BioSignal Program, Subteam for BioSignal Integration, RIKEN BioResource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba 305-0074, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Obata
authors.affiliation: Technology and Development Team for BioSignal Program, Subteam for BioSignal Integration, RIKEN BioResource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba 305-0074, Japan.
authors.forename: Takahiro S
authors.initials: TS
authors.lastname: Doi
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003713:Dendritic Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism*; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D020569:Proto-Oncogene Proteins c-rel / Q000037:antagonists & inhibitors*
chemical_list: D017931:DNA Primers; D053759:Interleukin-23; D052003:NF-kappa B p52 Subunit; D020569:Proto-Oncogene Proteins c-rel
keywords: Cytokines; Dendritic cells; Gene Regulation; NF-κB; c-Rel; p100