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

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

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Authors

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

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Info

Original languageEnglish
Pages333-338
Number of pages6
JournalCurrent Biology
Journal publication date23 Feb 2010
Volume20
Issue4
DOIs
StatePublished

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.

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