Active repression of antiapoptotic gene expression by RelA(p65) NF-kB

Kirsteen J. Campbell, Sonia Rocha, Neil D. Perkins

    Research output: Contribution to journalArticle

    327 Citations (Scopus)

    Abstract

    With the emerging role of NF-?B in cancer it is important that its responses to stimuli relevant to tumor progression and therapy are understood. Here, we demonstrate that NF-?B induced by cytotoxic stimuli, such as ultraviolet light (UV-C) and the chemotherapeutic drugs daunorubicin/doxorubicin, is functionally distinct to that seen with the inflammatory cytokine TNF and is an active repressor of antiapoptotic gene expression. Surprisingly, these effects are mediated by the RelA(p65) NF-?B subunit. Furthermore, UV-C and daunorubicin inhibit TNF-induced NF-?B transactivation, indicating that this is a dominant effect. Consistent with this, mechanistic studies reveal that UV-C and daunorubicin induce the association of RelA with histone deacetylases. RelA can therefore be both an activator and repressor of its target genes, dependent upon the manner in which it is induced. This has important implications for the role of NF-?B in tumorigenesis and the use of NF-?B inhibitors in cancer therapy.
    Original languageEnglish
    Pages (from-to)853-865
    Number of pages13
    JournalMolecular Cell
    Volume13
    Issue number6
    DOIs
    Publication statusPublished - Mar 2004

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    Daunorubicin
    NF-kappa B
    Gene Expression
    Neoplasms
    Histone Deacetylases
    Ultraviolet Rays
    Doxorubicin
    Transcriptional Activation
    Carcinogenesis
    Cytokines
    Therapeutics
    Pharmaceutical Preparations
    Genes

    Cite this

    Campbell, Kirsteen J. ; Rocha, Sonia ; Perkins, Neil D. / Active repression of antiapoptotic gene expression by RelA(p65) NF-kB. In: Molecular Cell. 2004 ; Vol. 13, No. 6. pp. 853-865.
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    Active repression of antiapoptotic gene expression by RelA(p65) NF-kB. / Campbell, Kirsteen J.; Rocha, Sonia; Perkins, Neil D.

    In: Molecular Cell, Vol. 13, No. 6, 03.2004, p. 853-865.

    Research output: Contribution to journalArticle

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