Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis

Bjorn Schumacher, Momoyo Hanazawa, Min-Ho Lee, Sudhir Nayak, Katrin Volkmann, Randall Hofmann, Michael Hengartner, Tim Schedl, Anton Gartner

    Research output: Contribution to journalArticle

    154 Citations (Scopus)

    Abstract

    p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.
    Original languageEnglish
    Pages (from-to)357-368
    Number of pages12
    JournalCell
    Volume120
    Issue number3
    DOIs
    Publication statusPublished - Feb 2005

    Fingerprint

    DNA Damage
    Genes
    Apoptosis
    Germ Cells
    DNA
    Cells
    Genomic Instability
    p53 Genes
    3' Untranslated Regions
    Transcription
    Tumor Suppressor Genes
    Gene expression
    Tumors
    Transcription Factors
    Messenger RNA
    Mutation
    Neoplasms
    Proteins

    Cite this

    Schumacher, B., Hanazawa, M., Lee, M-H., Nayak, S., Volkmann, K., Hofmann, R., ... Gartner, A. (2005). Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell, 120(3), 357-368. https://doi.org/10.1016/j.cell.2004.12.009
    Schumacher, Bjorn ; Hanazawa, Momoyo ; Lee, Min-Ho ; Nayak, Sudhir ; Volkmann, Katrin ; Hofmann, Randall ; Hengartner, Michael ; Schedl, Tim ; Gartner, Anton. / Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. In: Cell. 2005 ; Vol. 120, No. 3. pp. 357-368.
    @article{f36e4978408f47faaae6079fb19d9bf3,
    title = "Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis",
    abstract = "p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.",
    author = "Bjorn Schumacher and Momoyo Hanazawa and Min-Ho Lee and Sudhir Nayak and Katrin Volkmann and Randall Hofmann and Michael Hengartner and Tim Schedl and Anton Gartner",
    note = "dc.publisher: Elsevier",
    year = "2005",
    month = "2",
    doi = "10.1016/j.cell.2004.12.009",
    language = "English",
    volume = "120",
    pages = "357--368",
    journal = "Cell",
    issn = "0092-8674",
    publisher = "Elsevier",
    number = "3",

    }

    Schumacher, B, Hanazawa, M, Lee, M-H, Nayak, S, Volkmann, K, Hofmann, R, Hengartner, M, Schedl, T & Gartner, A 2005, 'Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis', Cell, vol. 120, no. 3, pp. 357-368. https://doi.org/10.1016/j.cell.2004.12.009

    Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. / Schumacher, Bjorn; Hanazawa, Momoyo; Lee, Min-Ho; Nayak, Sudhir; Volkmann, Katrin; Hofmann, Randall; Hengartner, Michael; Schedl, Tim; Gartner, Anton.

    In: Cell, Vol. 120, No. 3, 02.2005, p. 357-368.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis

    AU - Schumacher, Bjorn

    AU - Hanazawa, Momoyo

    AU - Lee, Min-Ho

    AU - Nayak, Sudhir

    AU - Volkmann, Katrin

    AU - Hofmann, Randall

    AU - Hengartner, Michael

    AU - Schedl, Tim

    AU - Gartner, Anton

    N1 - dc.publisher: Elsevier

    PY - 2005/2

    Y1 - 2005/2

    N2 - p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.

    AB - p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.

    U2 - 10.1016/j.cell.2004.12.009

    DO - 10.1016/j.cell.2004.12.009

    M3 - Article

    VL - 120

    SP - 357

    EP - 368

    JO - Cell

    JF - Cell

    SN - 0092-8674

    IS - 3

    ER -

    Schumacher B, Hanazawa M, Lee M-H, Nayak S, Volkmann K, Hofmann R et al. Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell. 2005 Feb;120(3):357-368. https://doi.org/10.1016/j.cell.2004.12.009