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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

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DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death

D Gozuacik1, S Bialik, T Raveh

  • 1Department of Molecular Genetics, Rehovot 76100, Israel.

Cell Death and Differentiation
|September 23, 2008
PubMed

Insights

Death-associated protein kinase (DAPk) is crucial for endoplasmic reticulum (ER) stress-induced cell death. DAPk deficiency protects mice and cells from ER stress, highlighting DAPk

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Endoplasmic reticulum (ER) stress disrupts cellular homeostasis.
  • The unfolded protein response (UPR) attempts to correct ER damage.
  • Unresolved ER stress triggers cell death pathways.

Purpose of the Study:

  • To identify key molecular components in ER stress-induced cell death.
  • To investigate the role of death-associated protein kinase (DAPk) in this process.

Main Methods:

  • Utilized DAPk knockout (DAPk-/-) mice and primary fibroblasts.
  • Administered ER stress-inducers like tunicamycin.
  • Assessed caspase activation, autophagy induction, and cell viability.
  • Investigated DAPk catalytic activity regulation via phosphorylation.

Main Results:

  • DAPk-/- mice and fibroblasts exhibited protection against ER stress-induced kidney damage and cell death.
  • Caspase activation and autophagy induction were significantly reduced in DAPk-deficient cells.
  • Autophagy acts as a secondary cell death mechanism alongside apoptosis in ER stress.
  • ER stress enhances DAPk activity by dephosphorylating Ser(308) via a PP2A-like phosphatase.

Conclusions:

  • DAPk is a critical mediator of ER stress-induced cell death.
  • DAPk integrates ER stress signals, directing them towards both caspase activation and autophagy.
  • Targeting DAPk may offer therapeutic strategies for conditions involving ER stress.

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