A Novel IκB Protein, IκB-ζ, Induced by Proinflammatory Stimuli, Negatively Regulates Nuclear Factor-κB in the Nuclei

Soh Yamazaki, Tatsushi Muta, Koichiro Takeshige

Research output: Contribution to journalArticlepeer-review

208 Citations (Scopus)

Abstract

The transcription factor nuclear factor-κB (NF-κB) plays crucial roles in a wide variety of cellular functions and its activity is strictly regulated by cytosolic inhibitors known as IκBs. We here report a new member of the IκB protein family, IκB-ζ, harboring six ankyrin repeats at its carboxyl terminus. IκB-ζ mRNA is strongly induced after stimulation by lipopolysaccharide. The induction of IκB-ζ is also observed by stimulation with interleukin-1β but not by tumor necrosis factor-α. In contrast to cytosolic IκB-α, -β, and -ε, the induced IκB-ζ localizes in the nucleus via its amino-terminal region, which shows no homology with other proteins. Transiently expressed IκB-ζ inhibits the NF-κB activity without affecting the nuclear translocation of NF-κB upon stimulation. The expressed IκB-ζ preferentially associates with the NF-κB subunit p50 rather than p65 and recombinant IκB-ζ proteins inhibit the DNA binding of the p65/p50 heterodimer and the p50/p50 homodimer. Thus, IκB-ζ negatively regulates NF-κB activity in the nucleus, possibly in order to prevent excessive inflammation. Moreover, transfection of IκB-ζ renders cells more susceptible to apoptosis induced by tumor necrosis factor-α. The proapoptotic activity of IκB-ζ further suggests that it might be one of key regulators for inflammation and other biologically relevant processes.

Original languageEnglish
Pages (from-to)27657-27662
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number29
DOIs
Publication statusPublished - 2001 Jul 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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