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 language | English |
|---|---|
| Pages (from-to) | 248-254 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 283 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2001 |
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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 journal › Article
}
TY - JOUR
T1 - A MEK inhibitor, PD98059 enhances IL-1-induced NF-κB activation by the enhanced and sustained degradation of IκBα
AU - Tago, Megumi
AU - Tago, Kenji
AU - Sonoda, Yoshiko
AU - Tominaga, Shin ichi
AU - Kasahara, Tadashi
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - ERK
KW - IκBα
KW - Interleukin-1
KW - MEK
KW - NF-κB
KW - PD98059
KW - Proteasome
UR - http://www.scopus.com/inward/record.url?scp=0034789898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034789898&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2001.4759
DO - 10.1006/bbrc.2001.4759
M3 - Article
VL - 283
SP - 248
EP - 254
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -