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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway

Junichi Hitomi1, Dana E Christofferson, Aylwin Ng

  • 1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Cell
|December 27, 2008
PubMed

Insights

Researchers identified 432 genes regulating necroptosis, a cell death pathway. This study defines the signaling network controlling necroptosis and apoptosis, revealing key regulators in innate immunity.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Death receptor agonists like FasL and TNFalpha trigger either apoptosis or necroptosis.
  • Necroptosis is a programmed necrosis dependent on RIP1 kinase, occurring in cells lacking apoptotic machinery.

Purpose of the Study:

  • To identify genes regulating necroptosis using a genome-wide screen.
  • To elucidate the signaling network controlling the bifurcation between apoptosis and necroptosis.

Main Methods:

  • Genome-wide siRNA screen to identify necroptosis regulators.
  • Analysis of gene expression enrichment in specific biological systems.
  • Identification of genes involved in both necroptosis and apoptosis.

Main Results:

  • A set of 432 genes regulating necroptosis was identified.
  • 32 genes acting downstream or as regulators of RIP1 kinase were found.
  • 7 genes were identified as common regulators of both necroptosis and apoptosis.
  • Gene expression enrichment was observed in immune and nervous systems.
  • Bmf, a Bcl-2 family member, was found essential for necroptosis.

Conclusions:

  • A comprehensive signaling network regulating necroptosis has been defined.
  • The study clarifies the molecular mechanisms controlling the switch between necroptosis and apoptosis.
  • Necroptosis regulation involves an extensive network related to innate immunity.

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