Positive and negative regulation of nuclear factor-κB-mediated transcription by IκB-ζ, an inducible nuclear protein

Masaiwa Motoyama, Soh Yamazaki, Akiko Eto-Kimura, Koichiro Takeshige, Tatsushi Muta

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

IκB-ζ is an inducible nuclear protein that interacts with nuclear factor-κB (NF-κB) via its carboxyl-terminal ankyrin-repeats. Previous studies using an NF-κB reporter have shown that IκB-ζ inhibits the activity of NF-κB. In the present study, we dissected the amino-terminal region of IκB-ζ, which shows no homology to any other proteins. Indirect immunofluorescence studies demonstrated the presence of a bipartite nuclear localization signal spanning amino acids 163-178. Using GAL4 fusion proteins, we found that internal fragments containing amino acids 329-402 possessed intrinsic transcriptional activation activity. Interestingly, the activity was not detected in GAL4 fusion proteins of the full-length IκB-ζ. On the other hand, the GAL4-dependent transcriptional activity was generated by co-expression of the GAL4-NF-κB p50 subunit fusion protein and the full-length. IκB-ζ, neither of which exhibited the activity on their own. A new splicing variant, IκB-ζ(D), with a deletion of amino acids 236-429, was found to lack transactivation activity. Forced expression of IκB-ζ, but not IκB-ζ(D), augmented interleukin-6 production, indicating the functional significance of the transactivation activity. In contrast, tumor necrosis factor-α production was inhibited by expression of IκB-ζ, highlighting the dual functions of this molecule. These results indicate that IκB-ζ harbors latent transcriptional activation activity, and that the activity is expressed upon interaction with the NF-κB p50 subunit. In addition to the inhibitory activity on NF-κB-mediated transcription, the transcriptional activation activity of IκB-ζ should be crucial for the regulation of inflammation.

Original languageEnglish
Pages (from-to)7444-7451
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number9
DOIs
Publication statusPublished - 2005 Mar 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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