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    Loss of IκB-β Is Associated with Prolonged NF-κB Activity in Human Glial Cells


    Bourke, Emer and Kennedy, Eugene J. and Moynagh, Paul N. (2000) Loss of IκB-β Is Associated with Prolonged NF-κB Activity in Human Glial Cells. Journal of Biological Chemistry, 275 (51). pp. 39996-40002. ISSN 0021-9258

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    Abstract

    Nuclear factor-κB (NF-κB) is an inducible transcription factor central in the regulation of expression of a wide variety of genes and synthesis of several proteins involved in the generation of the immune response and inflammatory processes. In resting cells, NF-κB is maintained in an inactive state through cytoplasmic retention by IκB inhibitors. Stimulation of cells with a wide variety of inducers results in proteolytic degradation of these IκB proteins, leading to activation of NF-κB. The present study shows that interleukin-1 (IL-1) causes persistent activation of NF-κB in glial cells. Stimulation with IL-1 also causes rapid but transient degradation of IκB-α and IκB-ε. However, NF-κB remains active even after these IκB isoforms have returned to control levels. In contrast, the IκB-β isoform fails to reappear following its initial degradation by IL-1, coincident with sustained activation of NF-κB. In addition, in vivo overexpression of the various IκB isoforms revealed that IκB-β is the only isoform that has the ability to inhibit IL-1-induced NF-κB-driven transcription. The findings also suggest that the inability of IκB-α and IκB-ε to modulate NF-κB activity is due to their modification in vivo. These findings indicate that IκB-β is the key regulator of the activity of NF-κB in human glial cells.

    Item Type: Article
    Additional Information: This research was originally published in the Journal of Biological Chemistry. Bourke, E., Kennedy, E.J. and Moynagh, P.N. (2000) 'Loss of Ikappa B-beta is associated with prolonged NF-kappa B activity in human glial cells'. 275 :39996-40002
    Keywords: IκB-β; Prolonged NF-κB Activity; Human Glial Cells;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7195
    Identification Number: https://doi.org/10.1074/jbc.M007693200
    Depositing User: Professor Paul Moynagh
    Date Deposited: 18 Jul 2016 09:08
    Journal or Publication Title: Journal of Biological Chemistry
    Publisher: American Society for Biochemistry and Molecular Biology
    Refereed: Yes
    Funders: Health Research Board (HRB), Enterprise Ireland (EI), European Commission
    URI:

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