Epoxyquinol B, a naturally occurring pentaketide dimer, inhibits NF-κB signaling by crosslinking TAK1

Hiroshi Kamiyama, Takeo Usui, Hiroaki Sakurai, Mitsuru Shoji, Yujiro Hayashi, Hideaki Kakeya, Hiroyuki Osada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Several epoxyquinoids interfere with NF-κB signaling by targeting IKKβ or NF-κB. We report that epoxyquinol B (EPQB), classified as an epoxyquiniod, inhibits NF-κB signaling through inhibition of the TAK1 complex, a factor upstream of IKKβ and NF-κB. cDNA microarray analysis revealed that EPQB decreased TNF-α-induced expression of NF-κB target genes. EPQB covalently bound to a recombinant TAK1-TAB1 fusion protein in vitro, and inhibited its kinase activity. Furthermore, in vitro/in situ treatment with EPQB resulted in a ladder-like hypershift of TAK1 protein bands. We reported recently that EPQB crosslinks proteins via cysteine residues by opening its two epoxides, and our current results suggest that EPQB inhibits NF-κB signaling by crosslinking TAK1 itself or TAK1 through other proteins.

Original languageEnglish
Pages (from-to)1894-1900
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume72
Issue number7
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Crosslink
  • Epoxyquinol B
  • NF-κB
  • TAK1

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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