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Published on: March 5, 2018

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation

T Mochizuki1, C Kitanaka, K Noguchi

  • 1Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.

Oncogene
|October 23, 1997
PubMed

Insights

Pim-1 kinase, not inhibiting apoptosis, actually stimulates c-Myc-induced cell death in fibroblasts. This occurs via enhanced caspase-3 activation, requiring Pim-1

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Pim-1 oncoprotein, a serine/threonine kinase, is implicated in lymphomagenesis alongside c-Myc.
  • The cooperative mechanism between Pim-1 and c-Myc in transformation is poorly understood.
  • It was hypothesized that Pim-1 inhibits apoptosis, similar to Bcl-2, contributing to transformation.

Purpose of the Study:

  • To investigate the role of Pim-1 expression in c-Myc-mediated apoptosis.
  • To determine if Pim-1 inhibits or stimulates apoptosis induced by c-Myc in Rat-1 fibroblasts.
  • To elucidate the molecular mechanism by which Pim-1 influences c-Myc-driven cell death.

Main Methods:

  • Utilized Rat-1 fibroblasts subjected to serum deprivation.
  • Assessed the impact of Pim-1 expression on c-Myc-mediated apoptosis.
  • Employed caspase inhibitors to evaluate the role of caspase-3 (CPP32)-like proteases.
  • Used a kinase-defective Pim-1 mutant to assess the requirement of kinase activity.

Main Results:

  • Pim-1 expression significantly stimulated, rather than inhibited, c-Myc-mediated apoptosis.
  • Pim-1 enhanced the activation of caspase-3 (CPP32)-like proteases, a key step in apoptosis.
  • Apoptosis stimulation was abolished by caspase inhibition, confirming the pathway.
  • Kinase-defective Pim-1 mutants did not stimulate apoptosis, highlighting the necessity of Pim-1's kinase activity.
  • Pim-1 alone did not induce apoptosis without c-Myc overexpression.

Conclusions:

  • Pim-1 oncoprotein acts as a serine/threonine kinase that stimulates c-Myc-induced apoptosis in Rat-1 fibroblasts.
  • The pro-apoptotic effect of Pim-1 occurs upstream of caspase-3 activation.
  • Pim-1 may cooperate with c-Myc in transformation by phosphorylating factors regulating shared apoptotic and transformation pathways.

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