title: Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages.
abstract: COP9 plays a role in plant innate immunity. The role of COP9 in mammalian innate immune responses is unknown. Here, we show that the COP9 signalosome subunit 5 (CSN5) is required for activation of proinflammatory kinases p38 and Erk and for down-regulation of the expression of genes regulated by nuclear factor E2-related factor 2. Mice with myeloid-specific CSN5 deficiency have lower mortality in polymicrobial sepsis. CSN5 is required for both Toll-like receptor (TLR) and reactive oxygen species-mediated deneddylation of Cul3, which is essential for Cul3/Keap1-mediated degradation of nuclear factor E2-related factor 2. On the basis of our results COP9 subunit CSN5 is considered to be an essential component of mammalian innate immunity.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.forename: Ruggero
authors.initials: R
authors.lastname: Pardi
authors.forename: William
authors.initials: W
authors.lastname: Cheadle
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiang
authors.forename: Shuangyin
authors.initials: S
authors.lastname: Zhang
authors.forename: Spandan V
authors.initials: SV
authors.lastname: Shah
authors.forename: William
authors.initials: W
authors.lastname: Grizzle
authors.forename: Donald
authors.initials: D
authors.lastname: Miller
authors.forename: John
authors.initials: J
authors.lastname: Mountz
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D044842:Cullin Proteins / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010447:Peptide Hydrolases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; C503646:Cul3 protein, mouse; D044842:Cullin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051193:Toll-Like Receptors; D010447:Peptide Hydrolases; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex