NF-KB(pSo/p65)PATHWAY TN TNFR GRADO LCST CourtesyofTheProteinLounge(http://www.proteinlounge.com).Usedwithpermission NF-kappaB transcription factors play an important role in the regulation of immune response, embryo and cell lineage o.velopment, cell apoptosis, inf lammation, cell-cycle progression, oncogenesis, viral replication, and various autoimmune The activation of NF-kappaB is thought to be part of a stress response as it is activated by a variety of stimuli that include growth factors, cytokines, lymphokines, UV, pharmacological agents, and other stresses. In its inactive form NF- cappaB is sequestered in the cytoplasm, bound by members of the IkappaB family of inhibitor proteins. The various stimuli that activate NF-kappaB cause phosphorylation of ikappaB, which is followed by its ubiquitination and subsequent degradation. IkB proteins are phosphorylated by a IkappaB kinase complex consisting of IKKalpha, IKKbeta, and IKKgamma, This phosphorylation results in the exposure of the nuclear localization signals (NLS)on the NF-kappaB subunits and the subsequent translocation of the molecule to the nucleus. In the nucleus, NF-kappaB binds with a consensus sequence GACTTTCC-3) of various genes, A total of five NF-kappaB subunits that form dimers have been identified in mammalian cell; RelA (p65), p50. RelB, c-Rel and p52. The most common and best characterized form of NF-kappaB is the p65-p50 heterdimer Each dimer combination exhibits diff DNA binding affinity and transactivation potential NF is one of the most potent physiological inducers of NF-kappaB, mediating inf lammation, cellular immune response, an affects the functions of virtually every cell type, tNF has also been shown to protect several cell types against apoptosis. suggesting that NF-kappaB could participate in resistance to cancer treatment. IL-1 has similar downstream affects through NF-kappaB, including immunoregulation, proinflammatory, and hematopoietic activities. LPs(bacterial lipopolysaccharide)activates NF-kappaB through the Toll-Like receptors, and induces the transcription of various nterleukins (e.g. IL-1)and cytokines(e.g. TNF)as a immune response against the bacteria.NF-kappaB transcription factors play an important role in the regulation of immune response, embryo and cell lineage development, cell apoptosis, inflammation, cell-cycle progression, oncogenesis, viral replication, and various autoimmune diseases. The activation of NF-kappaB is thought to be part of a stress response as it is activated by a variety of stimuli that include growth factors, cytokines, lymphokines, UV, pharmacological agents, and other stresses. In its inactive form NF￾kappaB is sequestered in the cytoplasm, bound by members of the IkappaB family of inhibitor proteins. The various stimuli that activate NF-kappaB cause phosphorylation of IkappaB, which is followed by its ubiquitination and subsequent degradation. IkB proteins are phosphorylated by a IkappaB kinase complex consisting of IKKalpha, IKKbeta, and IKKgamma. This phosphorylation results in the exposure of the nuclear localization signals (NLS) on the NF-kappaB subunits and the subsequent translocation of the molecule to the nucleus. In the nucleus, NF-kappaB binds with a consensus sequence (5‛ GGGACTTTCC-3‛) of various genes, activating their transcription. A total of five NF-kappaB subunits that form dimers have been identified in mammalian cell; RelA (p65), p50, RelB, c-Rel, and p52. The most common and best characterized form of NF-kappaB is the p65-p50 heterdimer. Each dimer combination exhibits differences in DNA binding affinity and transactivation potential. TNF is one of the most potent physiological inducers of NF-kappaB, mediating inflammation, cellular immune response, and affects the functions of virtually every cell type. TNF has also been shown to protect several cell types against apoptosis, suggesting that NF-kappaB could participate in resistance to cancer treatment. IL-1 has similar downstream affects through NF-kappaB, including immunoregulation, proinflammatory, and hematopoietic activities. LPS (bacterial lipopolysaccharide) activates NF-kappaB through the Toll-Like receptors, and induces the transcription of various interleukins (e.g. IL-1) and cytokines (e.g. TNF) as a immune response against the bacteria. Courtesy of The Protein Lounge (http://www.proteinlounge.com). Used with permission