Cell-Nonautonomous Regulation of C. elegans Germ Cell Death by kri-1

Shu Ito, Sebastian Greiss, Anton Gartner, W. Brent Derry

    Research output: Contribution to journalArticle

    37 Citations (Scopus)

    Abstract

    Programmed cell death (or apoptosis) is an evolutionarily conserved, genetically controlled suicide mechanism for cells that, when deregulated, can lead to developmental defects, cancers, and degenerative diseases [1, 2]. In C. elegans, DNA damage induces germ cell death by signaling through cep-1/p53, ultimately leading to the activation of CED-3/caspase [3-13]. It has been hypothesized that the major regulatory events controlling cell death occur by cell-autonomous mechanisms, that is, within the dying cell. In support of this, genetic studies in C. elegans have shown that the core apoptosis pathway genes ced-4l APAF-1 and ced-3/caspase are required in cells fated to die [9]. However, it is not known whether the upstream signals that activate apoptosis function in a cell-autonomous manner. Here we show that kri-1, an ortholog of KRIT1/CCM1, which is mutated in the human neurovascular disease cerebral cavernous malformation [14, 15], is required to activate DNA damage-dependent cell death independently of cep-1/p53. Interestingly, we find that kri-1 regulates cell death in a cell-nonautonomous manner, revealing a novel regulatory role for nondying cells in eliciting cell death in response to DNA damage.

    Original languageEnglish
    Pages (from-to)333-338
    Number of pages6
    JournalCurrent Biology
    Volume20
    Issue number4
    DOIs
    Publication statusPublished - 23 Feb 2010

    Keywords

    • DAMAGE-INDUCED APOPTOSIS
    • DNA-DAMAGE
    • CAENORHABDITIS-ELEGANS
    • CHECKPOINT PROTEIN
    • LIFE-SPAN
    • TUMOR-SUPPRESSOR
    • ENCODING KRIT1
    • GENE
    • CED-4
    • P53

    Cite this