Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

IKKi/IKK epsilon plays a key role in integrating signals induced by pro-inflammatory stimuli

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Kravchenko, Vladimir
  • Mathison, J. C.
  • Schwamborn, K.
  • Mercurio, F.
  • Ulevitch, Richard

publication date

  • 2003

journal

  • Journal of Biological Chemistry  Journal

abstract

  • We report that the product of the inducible gene encoding the kinase known as IKKi/IKKepsilon (IKKi) is required for expression of a group of genes up-regulated by pro-inflammatory stimuli such as bacterial endotoxin (lipopolysaccharide (LPS)). Here, using murine embryonic fibroblasts obtained from mice bearing deletions in IKK2, p65, and IKKi genes, we provide evidence to support a link between signaling through the NF-kappaB and CCAAA/enhancer-binding protein (C/EBP) pathways. This link includes an NF-kappaB-dependent regulation of C/EBPbeta and C/EBPdelta gene transcription and IKKi-mediated activation of C/EBP. Disruption of the NF-kappaB pathway results in the blockade of the inducible up-regulation of C/EBPbeta, C/EBPdelta, and IKKi genes. Cells lacking IKKi are normal in activation of the canonical NF-kappaB pathway but fail to induce C/EBPdelta activity and transcription of C/EBP and C/EBP-NF-kappaB target genes in response to LPS. In addition we show that, in response to LPS or tumor necrosis factor alpha, both beta and delta subunits of C/EBP interact with IKKi promoter, suggesting a feedback mechanism in the regulation of IKKi-dependent cellular processes. These data are among the first to provide insights into the biological function of IKKi.

subject areas

  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Cells, Cultured
  • Feedback
  • Humans
  • I-kappa B Kinase
  • Inflammation
  • Lipopolysaccharides
  • Mice
  • Mice, Knockout
  • NF-kappa B
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases
  • RNA Processing, Post-Transcriptional
  • RNA, Small Interfering
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M303001200

PubMed ID

  • 12736252
scroll to property group menus

Additional Document Info

start page

  • 26612

end page

  • 26619

volume

  • 278

issue

  • 29

©2019 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support