Multiple redox regulation in NF-κB transcription factor activation

Jacques Piette, Bernard Piret, Guiseppina Bonizzi, Sonia Schoonbroodt, Marie Paule Merville, Sylvie Legrand-Poels, Vincent Bours

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

The well-known Rel/NF-κB family of vertebrate transcription factors comprises a number of structurally related, interacting proteins that bind DNA as dimers and whose activity is regulated by subcellular location. This family includes many members (p50, p52, RelA, RelB, c-Rel, ...), most of which can form DNA-binding homo- or hetero-dimers. All Rel proteins contain a highly conserved domain of approximately 300 amino-acids, called the Rel homology domain (RH), which contains sequences necessary for the formation of dimers, nuclear localization, DNA binding and IκB binding. Nuclear expression and consequent biological action of the eukaryotic NF-κB transcription factor complex are tightly regulated through its cytoplasmic retention by ankyrin-rich inhibitory proteins known as IκB. The IκB proteins include a group of related proteins that interact with Rel dimers and regulate their activities. The interaction of a given IκB protein with a Rel complex can affect the Rel complex in distinct ways. In the best characterized example, IκB-α interacts with a p50/RelA (NF-κB) heterodimer to retain the complex in the cytoplasm and inhibit its DNA-binding activity. The NF-κB/IκB-α complex is located in the cytoplasm of most resting cells, but can be rapidly induced to enter the cell nucleus. Upon receiving a variety of signals, many of which are probably mediated by the generation of reactive oxygen species (ROS), IκB-α undergoes phosphorylation at serine residues by a ubiquitin-dependent protein kinase, is then ubiquitinated at nearby lysine residues and finally degraded by the proteasome, probably while still complexed with NF-κB. Removal of IκB-α uncovers the nuclear localization signals on subunits of NF-κB, allowing the complex to enter the nucleus, bind to DNA and affect gene expression. Like proinflammatory cytokines (e.g. IL-1, TNF), various ROS (peroxides, singlet oxygen, ...) as well as UV (C to A) light are capable of mediating NF-κB nuclear translocation, while the sensor molecules which are sensitive to these agents and trigger IκB-α proteolysis are still unidentified. We also show that a ROS-independent mechanism is activated by IL-1β in epithelial cells and seems to involve the acidic sphingomyelinase/ceramide transduction pathway.

Original languageEnglish
Pages (from-to)1237-1245
Number of pages9
JournalBiological Chemistry
Volume378
Issue number11
Publication statusPublished - Nov 1997

Fingerprint

Transcriptional Activation
Oxidation-Reduction
Transcription Factors
Dimers
Chemical activation
DNA
Reactive Oxygen Species
Proteins
Interleukin-1
Cytoplasm
Ankyrins
Proteolysis
Sphingomyelin Phosphodiesterase
Nuclear Localization Signals
Singlet Oxygen
Phosphorylation
Ceramides
Peroxides
Proteasome Endopeptidase Complex
Ubiquitin

Keywords

  • Cytokines
  • Nf-κB
  • Redox regulation
  • ROS

ASJC Scopus subject areas

  • Biochemistry

Cite this

Piette, J., Piret, B., Bonizzi, G., Schoonbroodt, S., Merville, M. P., Legrand-Poels, S., & Bours, V. (1997). Multiple redox regulation in NF-κB transcription factor activation. Biological Chemistry, 378(11), 1237-1245.

Multiple redox regulation in NF-κB transcription factor activation. / Piette, Jacques; Piret, Bernard; Bonizzi, Guiseppina; Schoonbroodt, Sonia; Merville, Marie Paule; Legrand-Poels, Sylvie; Bours, Vincent.

In: Biological Chemistry, Vol. 378, No. 11, 11.1997, p. 1237-1245.

Research output: Contribution to journalArticle

Piette, J, Piret, B, Bonizzi, G, Schoonbroodt, S, Merville, MP, Legrand-Poels, S & Bours, V 1997, 'Multiple redox regulation in NF-κB transcription factor activation', Biological Chemistry, vol. 378, no. 11, pp. 1237-1245.
Piette J, Piret B, Bonizzi G, Schoonbroodt S, Merville MP, Legrand-Poels S et al. Multiple redox regulation in NF-κB transcription factor activation. Biological Chemistry. 1997 Nov;378(11):1237-1245.
Piette, Jacques ; Piret, Bernard ; Bonizzi, Guiseppina ; Schoonbroodt, Sonia ; Merville, Marie Paule ; Legrand-Poels, Sylvie ; Bours, Vincent. / Multiple redox regulation in NF-κB transcription factor activation. In: Biological Chemistry. 1997 ; Vol. 378, No. 11. pp. 1237-1245.
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