title: Bidirectional regulation of NF-κB by reactive oxygen species: a role of unfolded protein response.
abstract: Nuclear factor-κB (NF-κB) is a transcription factor that plays a crucial role in coordinating innate and adaptive immunity, inflammation, and apoptotic cell death. NF-κB is activated by various inflammatory stimuli including peptide factors and infectious microbes. It is also known as a redox-sensitive transcription factor activated by reactive oxygen species (ROS). Over the past decades, various investigators focused on the role of ROS in the activation of NF-κB by cytokines and lipopolysaccharides. However, recent studies also suggested that ROS have the potential to repress NF-κB activity. Currently, it is not well addressed how ROS regulate activity of NF-κB in a bidirectional fashion. In this paper, we summarize evidence for positive and negative regulation of NF-κB by ROS, possible redox-sensitive targets for NF-κB signaling, and mechanisms underlying biphasic and bidirectional influences of ROS on NF-κB, especially focusing on a role of ROS-mediated induction of endoplasmic reticulum stress.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan. Electronic address: masanori@yamanashi.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D016328:NF-kappa B; D017382:Reactive Oxygen Species
keywords: 78-kDa glucose-regulated protein (BiP); ATF6; C/EBPβ; CCAAT/enhancer-binding protein homologous protein; CCAAT/enhancer-binding protein β; CHOP; DHMEQ; ER; ER stress response element; ER-associated degradation; ERAD; ERSE; Endoplasmic reticulum stress; GRP78; H/R; HDAC; HO-1; IKK; IL-1R; IRE1; IκB; IκB kinase; Keap-1; Kelch-like ECH-associated protein 1; LPS; NEMO; NF-κB; NF-κB essential modulator; NF-κB inducing kinase; NIK; Nrf2; PERK; PI3K; PKAc; PKB; PKD; PKR-like ER kinase; PP2A; RIP1; Reactive oxygen species; S1P; SH2-containing inositol 5′-phosphatase 1; SHIP-1; TNF receptor-associated factor; TNFR; TRAF; UPR; UPR element; UPRE; UV; Unfolded protein response; X-box-binding protein 1; XBP1; activating transcription factor 6; dehydroxymethylepoxyquinomicin; eIF2α; endoplasmic reticulum; eukaryotic translation initiation factor 2α; heme oxygenase 1; histone deacetylase; hypoxia/reoxygenation; inhibitor of NF-κB; inositol-requiring enzyme 1; interleukin-1 receptor; lipopolysaccharide; mTORC1; mammalian target of rapamycin complex 1; nuclear factor-E2-related factor 2; nuclear factor-κB; phosphatidylinositol 3-kinase; protein kinase A catalytic subunit; protein kinase B (Akt); protein kinase D; protein phosphatase 2A; receptor interacting protein 1; site-1 protease; tumor necrosis factor receptor; ultraviolet; unfolded protein response