The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors.
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Background: The transcriptional factor NFκB plays a pivotal role in triggering inflammation and autoimmune responses. We observed spontaneous development of myocarditis in NFκB p50-deficient NOD mi...
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SOCIETY OF CRITICAL CARE MEDICINE 32ND CRITICAL CARE CONGRESS SAN ANTONIO, TEXAS, USA JANUARY 28-FEBRUARY 2, 2003: ORAL/SANDWICH PRESENTATIONS: Poster Presentation: Basic Science: Sepsis Signal Transduction: PDF Only
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PubMed search was performed using the key words: NF-?B, nuclear factors, asthma. Articles were selected based on their relevance to this review.To review the literature regarding the involvement of the nuclear factor kappa-B (NF-?B) transcription factor in asthma.NF-?B is a critical transcription factor for the production of many inflammatory cytokines. NF-?B is associated with several diseases, including asthma, where there is an inflammation of the airways with cell infiltration. It is activated in bronchial asthmatic patient biopsies and active in the epithelium of the airways in mice after stimulation. It also participates in the maintenance of the chronic inflammatory response. NF-?B also acts synergistically with other transcription factors, to induce the maximal expression of genes involved with asthma. Activation of NF- ?B by several stimuli induces the release and degradation of the inhibitory protein I-?B from the dimeric complex followed by translocation of NF-?B to the nucleus.The NF-?B pathway is central to the pathogenesis of asthma. NF?B is an important therapeutic target for the treatment of asthma, including intermediate products on the signaling pathway and protein related to Rel. Alterations in the NF-?B signaling pathway are associated with the disease.
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The growth, differentiation, and development of an organism is orchestrated by the choreographed expression of a wide array of genes.The switching "on" and "off" of gene expression is the province of transcription factors, which operate singly or in association with other proteins.Usually transcription factors form families, whereas individual members perform specific, distinct, or similar tasks.One such family includes the R ~~/ N F -K B proteins (NF-KB), which have the unique property of being sequestered in the cytoplasm in association with inhibitory proteins called IKB.Activation and regulation of NF-KB are tightly controlled by IKB proteins.Through noncovalent association, the IKB proteins mask the nuclear localization signal (NLS) of NF-KB, thereby preventing NF-KB nuclear translocation.Upon stimulation with signaling molecules such as tumor necrosis factor a (TNFa) or lipopolysaccharide (LPS), NF-KB is released from IKB and translocated to the nucleus where it regulates gene transcription.Stimulation and activation of the NF-KB transcription factors do not require protein synthesis, thereby allowing rapid and efficient activation of target genes.This system is particularly utilized in immune, inflammatory, and acute phase responses where rapid activation of defense genes following exposure to pathogens such as bacteria and viruses is critical for survival of an organism.Many pathogenic viruses have evolved enhanced viral replication by including NF-KB target sites in their promoterlenhancer elements and producing proteins that activate NF-KB.Besides the immune responses and viral replication, NF-KB is also implicated in cellular proliferation and programmed cell death.Coincidentally, deregulation of NF-KB activity is directly associated with cellular transformation.The NF-KB homologs, Dorsal and Dif in the fruit fly Drosophila, are involved in the formation of embryonic polarity and insect immunity, respectively.Thus, the understanding of the regulation of RelINF-KB activity is of great interest to a wide variety of basic biological and medical fields.
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Nuclear factor kappa B (NF-kappa B) is common proinflammatory transcription factor involved in expression of c.a. 300 different genes. It is usually present in the cytosol as an inactive complex and upon activation translocates into the nucleus. The mechanisms of activation of NF-kappa B are complex and they involve several different signaling pathways and plethora of proteins. In this minireview we describe the main deciphered as well as suggested mechanisms regulating of NF-kappa B activity.
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