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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
Peer-reviewedYes

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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