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Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis

T Shirogane1, T Fukada, J M Muller

  • 1Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Japan.

Immunity
|January 8, 2000
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) activation by gp130 is crucial for cell cycle progression and survival. Pim-family proteins are key mediators in this pathway, working synergistically with c-Myc to drive cell proliferation and lymphomagenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Signal transducer and activator of transcription 3 (STAT3) activation by the cytokine receptor gp130 is essential for cell cycle progression and apoptosis resistance.
  • Understanding the downstream effectors of this pathway is critical for comprehending cell proliferation and oncogenesis.

Purpose of the Study:

  • To identify and characterize downstream targets of the gp130-STAT3 signaling pathway.
  • To elucidate the roles of Pim-family kinases and their targets in cell proliferation and survival.
  • To investigate the synergistic interaction between Pim and c-Myc in lymphomagenesis.

Main Methods:

  • Analysis of STAT3 target genes using molecular biology techniques.
  • Expression of wild-type and mutant forms of Pim-1 and valosine-containing protein (VCP).
  • Assessment of cell proliferation, apoptosis, and gene expression (e.g., bcl-2).

Main Results:

  • Pim-1 and Pim-2 were identified as direct targets of the gp130-STAT3 signaling pathway.
  • Expression of a kinase-defective Pim-1 mutant inhibited gp130-mediated cell proliferation.
  • Constitutive expression of Pim-1 and c-Myc fully restored STAT3-mediated cell cycle progression, anti-apoptosis, and bcl-2 expression.
  • Valosine-containing protein (VCP) was identified as a downstream target of Pim-1, and its mutant form induced apoptosis.

Conclusions:

  • Pim-family proteins are critical mediators of gp130-STAT3-driven cell proliferation.
  • Pim proteins, in conjunction with c-Myc, play a significant role in cell proliferation and lymphomagenesis.
  • VCP is a key downstream effector in the Pim-mediated signaling pathway, influencing cell survival.

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