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NF-κB is an inducible transcription factor that controls expression of diverse stress response genes. The entire mammalian NF-κB family is generated from a small cadre of five gene products that assemble with one another in various combinations to form active homo- and heterodimers. The ability of NF-κB to alter target gene expression is regulated at many levels. Chief among these regulatory mechanisms...
Nuclear Factor-κB (NF-κB)/Rel transcription factors form an integral part of innate immune defenses and are conserved throughout the animal kingdom. Studying the function, mechanism of activation and regulation of these factors is crucial for understanding host responses to microbial infections. The fruit fly Drosophila melanogaster has proved to be a valuable model system to study these evolutionarily...
Inflammatory responses to microbial and non-microbial stimuli involve coordinate changes in the expression of hundreds of genes. The inflammatory gene expression programs display two important features: first, alternative stimuli affect both a large set of common genes and a variable number of stimulus-specific genes. Second, different genes are activated with different kinetics over several hours...
The IKK kinase complex is the core element of the NF-κB cascade. It is essentially made of two kinases (IKKα and IKKβ) and a regulatory subunit, NEMO/IKKγ. Additional components may exist, transiently or permanently, but their characterization is still uncertain. In this review, we will focus on the NEMO molecule, and describe the results which have been obtained, and the hypotheses which have been...
NF-κB transcription factors are critical regulators of many biological processes such as innate and adaptive immune responses, inflammation, cell proliferation and programmed cell death. This versatility necessitates a highly complex and tightly coordinated control of the signaling pathways leading to their activation. Here, we review the role of proteolysis in the regulation of NF-κB activity, more...
Members of the NF-κB transcription factor family play a critical role in the development of innate immunity. Upon recognition of pathogen infections or tissue damage, the NF-κB pathway is strongly activated by cellular pattern recognition receptors, including Toll-like receptors and multiple cytosolic receptors such as RIG-I-like helicases and NOD family proteins. NF-κB is required not only for the...
NF-κB is well characterized as a primary mediator of inflammatory responses during infection and immune reactions, but it has recently become evident that NF-κB also mediates a potent cytoprotective, homeostatic function under basal conditions. This role is especially evident in the mammalian intestine, which is challenged not only with a range of microbial pathogens, but is also in constant contact...
Since the initial cloning of RelA and its close relationship to c-Rel, the cellular homolog of the viral oncoprotein v-Rel, the nuclear factor κB (NF-κB) signaling pathway and its upstream activating kinase complex (IκB-kinase) have been suspected to play a major role in tumorigenesis. This was further corroborated by the discovery of oncogenic mutations in NF-κB proteins in certain lymphoid malignancies...
Macrophages are tissue resident phagocytes with important roles in development, wound healing, and inflammation. There is enormous heterogeneity in macrophage phenotype, from ‘classically’ activated macrophages that have important roles in inflammation and innate immunity, to ‘alternative’ macrophage activation that is associated with wound healing, angiogenesis, and immune-suppression. Most, if not...
The role of the NF-κB signaling pathway in liver cancer is complex. While some evidence suggests that in the liver, like in many other organ systems, NF-κB is oncogenic, there is strong evidence showing that in certain liver cancer models NF-κB suppresses tumorigenesis. These contrasting findings cannot be dismissed on technicalities and are likely due to the complex nature of the NF-κB response....
NF-κB is a pivotal transcription factor that controls cell survival and proliferation in diverse physiological processes. The activity of NF-κB is tightly controlled through its cytoplasmic sequestration by specific inhibitors, IκBs. Various cellular stimuli induce the activation of an IκB kinase, which phosphorylates IκBs and triggers their proteasomal degradation, causing nuclear translocation of...
As described extensively in this issue, NF-κB transcription factors regulate a number of important physiological processes, including inflammation and immune responses, cell growth and survival, and the expression of certain viral genes. Moreover, NF-κB activity is elevated in and contributes to the pathology of several human diseases, including many cancers and chronic inflammatory diseases. Therefore,...
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