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Paeonol-mediated apoptosis of hepatocellular carcinoma cells by NF-κB pathway.
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NFkB is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NFkB is is activated by various intra and extra cellular stimuli such as cytokines, oxidant free radicals, ultraviolet irradiation, and bacterial or viral products. NFkB is a family of transcription factors that consists of homo and heterodimers of NFkB1/p50 and RelA/p65 subunits, and controls a variety of cellular events including development and immune responses. All members share a conserved amino terminus domain that includes dimerization, nuclear localization, and DNA binding regions, and a carboxy terminal transactivation domain. Serines 529 and 536 in the transactivation domain of RelA/p65 are phosphorylated in response to several stimuli including phorbol ester, IL1 alpha and TNF alpha as mediated by IkB kinase and p38 MAPK. Phosphorylation of serines 529 and 536 is critical for RelA/p65 transcriptional activity. Activated NFkB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFkB has been associated with a number of inflammatory diseases while persistent inhibition of NFkB leads to inappropriate immune cell development or delayed cell growth. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. This antibody can bind both p105 and p50 isoforms of NFKB1.