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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

Cytokine-mediated cell survival

Toshiya Inaba1

  • 1Department of Molecular Oncology & Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. tinaba@hiroshima-u.ac.jp

International Journal of Hematology
|November 16, 2004
PubMed

Insights

Cytokine signaling pathways regulate cell survival by controlling Bim, a key cell death regulator. Cytokines modulate Bim expression at multiple levels, impacting hematopoietic and neuronal cell survival.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Cytokine receptor signaling is crucial for cell survival.
  • Two key pathways, JAK/STATs/Bcl-xL and Ras/PI3-K, support cell survival.
  • The Ras/PI3-K pathway is essential for long-term survival via Bim down-regulation.

Purpose of the Study:

  • To investigate the role of Bim in cytokine-mediated cell survival.
  • To elucidate the regulatory mechanisms of Bim expression by cytokines.
  • To understand Bim's implication in leukemogenesis.

Main Methods:

  • Utilized the Baf-3 murine interleukin 3-dependent cell line.
  • Investigated cytokine regulation of Bim at mRNA and protein levels.
  • Examined Bim's subcellular localization and interaction with the dynein motor complex.

Main Results:

  • Bim, a BH3-only protein, is a critical mediator of cytokine-initiated cell survival.
  • Cytokines regulate Bim expression at transcriptional, post-transcriptional (mRNA stability), and post-translational (protein degradation) levels.
  • Regulation of Bim at the mRNA level is particularly important in hematopoiesis.
  • Bim is implicated in Bcr-Abl and receptor tyrosine kinase-driven leukemogenesis.

Conclusions:

  • Bim is a central regulator of cell survival in response to cytokine signaling.
  • Cytokine-induced cell survival involves intricate regulation of Bim expression and function.
  • Understanding these pathways offers insights into hematopoietic cell survival and leukemogenesis.

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