Journal ArticleDOI
Function and activation of NF-kappa B in the immune system.
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TLDR
The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, severe phase response, and radiation damage.Abstract:
NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes.read more
Citations
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Role of the IκB Kinase Complex in Oncogenic Ras- and Raf-Mediated Transformation of Rat Liver Epithelial Cells
TL;DR: A mechanism that contributes to the process of transformation of liver cells by oncogene Ras and Raf through the IκB kinase complex leading to constitutive activation of NF-κB is elucidated.
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Genetic and biochemical characterization of glycerol uptake in mycoplasma mycoides subsp. mycoides SC: its impact on H(2)O(2) production and virulence.
Edy M. Vilei,Joachim Frey +1 more
TL;DR: The efficient glycerol uptake system found in the virulent strain of the African cluster leads to a strong release of peroxide, a potential virulence factor which is lacking in the less virulent European strains.
Journal ArticleDOI
NADPH oxidase promotes NF-κB activation and proliferation in human airway smooth muscle
Sukhdev S. Brar,Thomas P. Kennedy,Anne Sturrock,Thomas P. Huecksteadt,Mark T. Quinn,Thomas M. Murphy,Pasquale Chitano,John R. Hoidal +7 more
TL;DR: It is suggested that an NADPH oxidase containing p22(phox) regulates growth-factor responsive human AWSM proliferation, and that the oxidase signals in part through activation of the prototypical redox-regulated transcription factor NF-kappaB.
Journal ArticleDOI
CLAP, a Novel Caspase Recruitment Domain-containing Protein in the Tumor Necrosis Factor Receptor Pathway, Regulates NF-κB Activation and Apoptosis *
Srinivasa M. Srinivasula,Manzoor Ahmad,Jun-Hsiang Lin,Jean-Luc Poyet,Teresa Fernandes-Alnemri,Philip N. Tsichlis,Emad S. Alnemri +6 more
TL;DR: The cloning of the cellular homolog of the equine herpesvirus-2 protein E10 is described and it is shown that both proteins regulate apoptosis and NF-κB activation.
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Drosophila larval neuromuscular junction: molecular components and mechanisms underlying synaptic plasticity.
TL;DR: The Drosophila larval neuromuscular junction provides a particularly useful model for investigating the roles of synaptic components in both structural and functional plasticity, and the powerful molecular genetics of this system makes it possible to uncover new synaptic components and signaling molecules, as well as their function in the intact organism.
References
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Book
Free radicals in biology and medicine
TL;DR: 1. Oxygen is a toxic gas - an introduction to oxygen toxicity and reactive species, and the chemistry of free radicals and related 'reactive species'
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Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.
TL;DR: It is shown that micromolar concentrations of H2O2 can induce the expression and replication of HIV‐1 in a human T cell line and suggests that diverse agents thought to activate NF‐kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI.
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Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
Ranjan Sen,David Baltimore +1 more
TL;DR: In this paper, an electrophoretic mobility shift assay with end-labeled DNA fragments was used to characterize proteins that bind to the immunoglobulin (Ig) heavy chain and the kappa light chain enhancers.
Journal ArticleDOI
The mechanism of action of cyclosporin A and FK506
TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
Journal ArticleDOI
An inducible transcription factor activates expression of human immunodeficiency virus in T cells
Gary J. Nabel,David Baltimore +1 more
TL;DR: Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-κB, with binding sites in the viral enhancer.