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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

Identification of proteolytic fragments from ErbB-2 that induce apoptosis

Oleg Tikhomirov1, Mikhail Dikov, Graham Carpenter

  • 1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.

Oncogene
|March 23, 2005
PubMed

Insights

Fragmentation of the ErbB-2 kinase domain induces apoptosis, a form of programmed cell death. Specific peptides from this domain trigger cell death independently of caspases, suggesting a novel cell death pathway.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Receptor tyrosine kinases (RTKs) like ErbB-2 are crucial in cell signaling, proliferation, differentiation, and cancer.
  • ErbB-2 dysregulation is implicated in oncogenesis, making it a significant target in cancer research.

Purpose of the Study:

  • To investigate the role of ErbB-2 kinase domain fragmentation in apoptosis.
  • To identify specific ErbB-2 fragments that can induce cell death.
  • To explore the mechanism of ErbB-2-induced apoptosis.

Main Methods:

  • Exogenous expression of ErbB-2 derived peptides and carboxy-terminal domains in cells.
  • Assessment of cell death using apoptosis hallmarks.
  • Treatment with pan-caspase inhibitor z-VAD-FMK to evaluate caspase-dependent pathways.

Main Results:

  • Fragmentation of the ErbB-2 kinase domain is critical for inducing apoptosis.
  • A 37-residue peptide from the ErbB-2 N-terminal lobe strongly induced apoptosis.
  • ErbB-2 carboxy-terminal domain expression did not induce apoptosis.
  • The induced cell death was not inhibited by z-VAD-FMK, suggesting a caspase-independent mechanism.
  • Similar fragments from other RTKs also induced cell death.

Conclusions:

  • Proteolytic fragmentation of RTK kinase domains can liberate apoptotic fragments.
  • These fragments can trigger cell death through a caspase-independent pathway.
  • This mechanism represents a novel pathway for accelerating cell death, with potential implications for cancer therapy.

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