Transcription factor NF-κB has attracted attention due to its important role in the regulation of the expression of a number of cellular genes involved in host defense,inflammation/immune responses,cytokine and growth factor regulation,cell survival,proliferation,and also in embryonic development and programmed cell death. In this review,we provide an overview of established TNF-α,TLR/IL-1R,TCR and BCR signaling pathways to NF-κB,the alternative NF-κB pathway,and the regulation of NF-κB transcriptional activity. Furthermore,we discuss on emphasis the cross-talks between NF-κB and other signaling pathways (TGF-β,p53,nuclear receptor family,Ras/MEK/MAPK...),which are very complex and remain to be understood. The activation or inhibition of NF-κB has effect on other signaling pathways. They compose a complex signaling network,in which many regulatory signals integrate systematically and coordinate transcriptional responses to the stimulations. So when NF-κB is used as an important target of drugs in human diseases,the pathological and physiological functions of related signal pathways also should be understood sufficiently.
IκB is an inhibitor of nuclear factor-kappa B(NF-κB) and presents in the majority of cells.Eightstructurally related members of the mammalian IκB family have been described: IκBα,IκBβ,IκBε,Bcl-3,IκBγ,IκBδ,p100 and p105.The ankyrin repeat domain of IκB can interact with NF-κB,and sequester NF-κB in the cytoplasm as in-active complexes.Most recently,IκBαhas been found to inhibit p53 tumor suppressor protein by binding p53 to form a cyto-plasmic p53.IκBαcomplex and studies have shown that p100 profoundly sensitizes cells to death-receptor-mediated ap-optosis.The current review is to describe the members of IκB family,their related signaling pathways,and their applicationin tumor therapy.
