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    Regulation of Toll-like receptor 4 signalling by A20 zinc finger protein


    O'Reilly, Susan M. and Moynagh, Paul N. (2003) Regulation of Toll-like receptor 4 signalling by A20 zinc finger protein. Biochemical and Biophysical Research Communications, 303 (2). pp. 586-593. ISSN 0006-291X

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    Abstract

    A20 is a zinc finger protein that renders cells resistant to apoptosis. However, the recent demonstration that A20-deficient mice develop severe inflammation and are hyper-responsive to LPS suggests that A20 may play a key role in regulating the inflammatory response. This study, for the first time, explores the likely mechanism by which A20 can regulate the pro-inflammatory effects of LPS. More specifically it characterises the ability of A20 to modulate TLR-4 signalling since TLR-4 acts as the signalling receptor system for LPS. Full length A20 inhibited the ability of TLR-4 to activate the transcription factors, NF-jB and AP-1, and induce the chemokine IL-8. The inhibitory capacity of A20 on NF-jB was localised to the C-terminal zinc finger domain of A20 whereas full length A20 was required to effect inhibition of AP-1 and IL-8. Furthermore full length and C-terminal A20 showed similar regulatory effects on MEKK-1 activation of NF-jB and AP-1 and induction of IL-8. The findings increase our mechanistic understanding of the anti-inflammatory effects of A20 and suggest that it modulates TLR-4 signalling at or downstream of MEKK-1.

    Item Type: Article
    Keywords: Inflammation; Signal transduction; Transcription factors; Toll-like receptor;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7208
    Identification Number: https://doi.org/10.1016/S0006-291X(03)00389-9
    Depositing User: Professor Paul Moynagh
    Date Deposited: 20 Jul 2016 16:02
    Journal or Publication Title: Biochemical and Biophysical Research Communications
    Publisher: Academic Press
    Refereed: Yes
    Funders: European Biotechnology 5th Framework Programme, Health Research Board (HRB), Enterprise Ireland (EI)
    URI:

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