Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages.

Academic Article

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.
  • Published In

  • Blood  Journal
  • Keywords

  • Animals, Antioxidants, COP9 Signalosome Complex, Cullin Proteins, Female, Immunity, Innate, Intracellular Signaling Peptides and Proteins, Lung, MAP Kinase Signaling System, Macrophage Activation, Macrophages, Male, Mice, Mice, Knockout, NF-E2-Related Factor 2, Peptide Hydrolases, Shock, Septic, Signal Transduction, Toll-Like Receptors, Up-Regulation
  • Digital Object Identifier (doi)

    Author List

  • Deng Z; Pardi R; Cheadle W; Xiang X; Zhang S; Shah SV; Grizzle W; Miller D; Mountz J; Zhang H-G
  • Start Page

  • 4796
  • End Page

  • 4804
  • Volume

  • 117
  • Issue

  • 18