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    Investigating nucleo-cytoplasmic shuttling of the human DEAD-box helicase DDX3


    Brennan, Ruth and Haap-Hoff, Antje and Gua, Lili and Gautier, Virginie and Long, Aideen and Schroeder, Martina (2018) Investigating nucleo-cytoplasmic shuttling of the human DEAD-box helicase DDX3. European Journal of Cell Biology, 97 (7). pp. 501-511. ISSN 0171-9335

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    Abstract

    The human DEAD-box helicase DDX3 is a multi-functional protein involved in the regulation of gene expression and additional non-conventional roles as signalling adaptor molecule that are independent of its enzymatic RNA remodeling activity. It is a nucleo-cytoplasmic shuttling protein and it has previously been suggested that dysregulation of its subcellular localization could contribute to tumourigenesis. Indeed, both tumour suppressor and oncogenic functions have been attributed to DDX3. In this study, we investigated the regulation of DDX3's nucleocytoplasmic shuttling. We confirmed that an N-terminal conserved Nuclear Export Signal (NES) is required for export of human DDX3 from the nucleus, and identified three regions within DDX3 that can independently facilitate its nuclear import. We also aimed to identify conditions that alter DDX3's subcellular localisation. Viral infection, cytokine treatment and DNA damage only induced minor changes in DDX3's subcellular distribution as determined by High Content Analysis. However, DDX3's nuclear localization increased in early mitotic cells (during prophase) concomitant with an increase in DDX3 expression levels. Our results are likely to have implications for the proposed use of (nuclear) DDX3 as a prognostic biomarker in cancer.

    Item Type: Article
    Additional Information: Cite as: Ruth Brennan, Antje Haap-Hoff, Lili Gu, Virginie Gautier, Aideen Long, Martina Schröder, Investigating nucleo-cytoplasmic shuttling of the human DEAD-box helicase DDX3, European Journal of Cell Biology, Volume 97, Issue 7, 2018, Pages 501-511, ISSN 0171-9335, https://doi.org/10.1016/j.ejcb.2018.08.001.
    Keywords: Cell cycle; DDX3X; DEAD-box helicase; Nuclear export; Nuclear import; Nucleo-cytoplasmic shuttling;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 13711
    Identification Number: https://doi.org/10.1016/j.ejcb.2018.08.001
    Depositing User: Martina Schroeder
    Date Deposited: 30 Nov 2020 17:17
    Journal or Publication Title: European Journal of Cell Biology
    Publisher: Elsevier
    Refereed: Yes
    URI:

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