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

Biochemical and Biophysical Research Communications
M FunakoshiT Kasahara

Abstract

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

References

Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·E EytanA Hershko
Feb 1, 1994·The Journal of Experimental Medicine·M A ReadT Collins
Jun 9, 1995·The Journal of Biological Chemistry·S A GreenfederG Ju
Apr 9, 1994·Lancet·A Mantovani, S Sozzani
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K MueggeS K Durum
Oct 1, 1993·Molecular and Cellular Biology·C Kunsch, C A Rosen
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Oct 3, 1996·Nature·Z CaoD V Goeddel
Mar 1, 1997·Molecular Biology Reports·S DawsonR J Mayer
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·N Li, M Karin
Apr 1, 1999·American Journal of Respiratory Cell and Molecular Biology·A B CarterG W Hunninghake

❮ Previous
Next ❯

Citations

Jan 31, 2009·Nature Reviews. Drug Discovery·Jia JiaYu Zong Chen
Mar 13, 2003·European Journal of Biochemistry·Megumi Funakoshi-TagoTadashi Kasahara
Jan 16, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Koichi InoueMasatoshi Hagiwara
Mar 12, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tadashi Kasahara
Apr 18, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Razao IssaKian Fan Chung
May 16, 2003·The Journal of Biological Chemistry·Megumi Funakoshi-TagoTadashi Kasahara
Jul 3, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin WangAnatoly V Grishin
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Iolanda D'AlimonteRenata Ciccarelli
Oct 3, 2006·The Journal of Biological Chemistry·Katarzyna M WilczynskaTomasz Kordula
Jan 24, 2006·International Immunopharmacology·Sachiko MatsuiTadashi Kasahara
Nov 28, 2002·Cytokine·Michael Kracht, Jeremy Saklatvala
Jul 25, 2021·International Journal of Molecular Sciences·Wonmin KoDong-Sung Lee

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.