THE NF-κB AND IκB PROTEINS: New Discoveries and Insights

Annual Review of Immunology - Tập 14 Số 1 - Trang 649-681 - 1996
Albert S. Baldwin1
1Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, and Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599

Tóm tắt

▪ Abstract  The transcription factor NF-κB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-κB is through interactions with an inhibitor protein called IκB. Recent evidence confirms the existence of multiple forms of IκB that appear to regulate NF-κB by distinct mechanisms. NF-κB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-κB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IκB. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-κB. In the nucleus, NF-κB dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-κB is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-κB activation, excitement in NF-κB research has been generated by the first report of a crystal structure for one form of NF-κB, the first gene knockout studies for different forms of NF-κB and of IκB, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-κB.

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Annual Review of Immunology

Tập 14 Số 1

649-681

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