The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor

Gaynor J. Bates, Samantha M. Nicol, Brian J. Wilson, Anne-Marie F. Jacobs, Jean-Christophe Bourdon, Julie Wardrop, David J. Gregory, David P. Lane, Neil D. Perkins, Frances V. Fuller-Pace

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    175 Citations (Scopus)

    Abstract

    The DEAD box RNA helicase, p68, has been implicated in various cellular processes and has been shown to possess transcriptional coactivator function. Here, we show that p68 potently synergises with the p53 tumour suppressor protein to stimulate transcription from p53-dependent promoters and that endogenous p68 and p53 co-immunoprecipitate from nuclear extracts. Strikingly, RNAi suppression of p68 inhibits p53 target gene expression in response to DNA damage, as well as p53-dependent apoptosis, but does not influence p53 stabilisation or expression of non-p53-responsive genes. We also show, by chromatin immunoprecipitation, that p68 is recruited to the p21 promoter in a p53-dependent manner, consistent with a role in promoting transcriptional initiation. Interestingly, p68 knock-down does not significantly affect NF-kappaB activation, suggesting that the stimulation of p53 transcriptional activity is not due to a general transcription effect. This study represents the first report of the involvement of an RNA helicase in the p53 response, and highlights a novel mechanism by which p68 may act as a tumour cosuppressor in governing p53 transcriptional activity.

    Original languageEnglish
    Pages (from-to)543-553
    Number of pages11
    JournalThe EMBO Journal
    Volume24
    Issue number3
    DOIs
    Publication statusPublished - 9 Feb 2005

    Keywords

    • DEAD box protein
    • DNA damage response
    • p53
    • p68
    • Transcriptional coactivator
    • Protein kinases metabolism
    • RNA helicases metabolism
    • Tumour suppressor protein p53 metabolism

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  • Cite this

    Bates, G. J., Nicol, S. M., Wilson, B. J., Jacobs, A-M. F., Bourdon, J-C., Wardrop, J., Gregory, D. J., Lane, D. P., Perkins, N. D., & Fuller-Pace, F. V. (2005). The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. The EMBO Journal, 24(3), 543-553. https://doi.org/10.1038/sj.emboj.7600550