A MEK inhibitor, PD98059 enhances IL-1-induced NF-κB activation by the enhanced and sustained degradation of IκBα

Megumi Tago, Kenji Tago, Yoshiko Sonoda, Shin ichi Tominaga, Tadashi Kasahara

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Interleukin-1 (IL-1) mediates numerous host responses through rapid activation of nuclear factor-κB (NF-κB), but signal pathways leading to the NF-κB activation appear to be complicated and multiplex. We propose a novel regulatory system for NF-κB activation by the extracellular signal-related kinase (ERK) pathway. In a human glioblastoma cell line, T98G, IL-1-induced NF-κB activation was significantly augmented by the pretreatment of a specific MEK inhibitor, PD98059. In contrast, ectopic expression of a constitutive activated form of Raf (v-Raf) reduced IL-1-induced NF-κB activation, and this inhibition was completely reversed by PD98059. Interestingly, PD98059 sustained IL-1-induced NF-κB DNA binding activity by an eletrophoretic mobility shift assay and also IκBα degradation, presumably by augmenting and sustaining the proteasome activation. Concomitantly, two NF-κB dependent genes, A20 and IκBα expression were prolonged with PD98059. These data suggested that MEK-ERK pathway exerts a regulatory effect on NF-κB activation, providing a novel insight on the role of MEK-ERK pathway.

Original languageEnglish
Pages (from-to)248-254
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume283
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

Mitogen-Activated Protein Kinase Kinases
Interleukin-1
Chemical activation
Degradation
Phosphotransferases
Electrophoretic Mobility Shift Assay
Proteasome Endopeptidase Complex
Glioblastoma
Signal Transduction
Cell Line
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
DNA
Assays
Genes
Cells

Keywords

  • ERK
  • IκBα
  • Interleukin-1
  • MEK
  • NF-κB
  • PD98059
  • Proteasome

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A MEK inhibitor, PD98059 enhances IL-1-induced NF-κB activation by the enhanced and sustained degradation of IκBα. / Tago, Megumi; Tago, Kenji; Sonoda, Yoshiko; Tominaga, Shin ichi; Kasahara, Tadashi.

In: Biochemical and Biophysical Research Communications, Vol. 283, No. 1, 2001, p. 248-254.

Research output: Contribution to journalArticle

Tago, Megumi ; Tago, Kenji ; Sonoda, Yoshiko ; Tominaga, Shin ichi ; Kasahara, Tadashi. / A MEK inhibitor, PD98059 enhances IL-1-induced NF-κB activation by the enhanced and sustained degradation of IκBα. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 283, No. 1. pp. 248-254.
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