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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

Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways

Tomoharu Fukumori1, Yukinori Takenaka, Natsuo Oka

  • 1Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

Cancer Research
|May 20, 2004
PubMed

Insights

Galectin-3 determines cell fate in CD95 (APO-1/Fas) signaling. This antiapoptotic molecule directs cells toward type I apoptosis, preventing mitochondrial involvement and promoting survival.

Area of Science:

  • Cell biology
  • Molecular biology
  • Immunology

Background:

  • CD95 (APO-1/Fas) receptor initiates apoptosis via two distinct pathways: type I (caspase-8 dependent) and type II (mitochondria dependent).
  • The specific pathway activated by apoptotic insults remains largely undetermined.
  • Galectin-3, an antiapoptotic protein, possesses a conserved motif similar to Bcl-2 family proteins.

Purpose of the Study:

  • To investigate the role of galectin-3 in regulating CD95 apoptotic signaling pathways.
  • To identify galectin-3 as a potential determinant of type I versus type II apoptosis.
  • To explore the interaction between galectin-3 and the CD95 receptor.

Main Methods:

  • Cellular expression analysis of galectin-3 in type I and type II apoptotic phenotypes.
  • Galectin-3 cDNA transfection into galectin-3 null cells to assess phenotypic changes.
  • In vivo co-immunoprecipitation assays to detect galectin-3 and CD95 complex formation.

Main Results:

  • Galectin-3 expression was exclusively observed in type I apoptotic cells.
  • Transfection of galectin-3 into type II cells induced a type I apoptotic phenotype.
  • Galectin-3 was identified as a novel binding partner of CD95 in vivo.

Conclusions:

  • Galectin-3 dictates the selection of the CD95 apoptotic signaling pathway.
  • Galectin-3 promotes a type I apoptotic response, favoring caspase-8 activation over mitochondrial pathways.
  • The interaction of galectin-3 with CD95 is a key mechanism controlling cell death decisions.

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