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

Immunity. 1999 Dec;11(6):709-19. doi: 10.1016/s1074-7613(00)80145-4.

Abstract

The activation of STAT3 by the cytokine receptor gp130 is required for both the G1 to S cell cycle transition and antiapoptosis. We found that Pim-1 and Pim-2 are targets for the gp130-mediated STAT3 signal. Expression of a kinase-defective Pim-1 mutant attenuated gp130-mediated cell proliferation. Constitutive expression of Pim-1 together with c-myc, another STAT3 target, fully compensated for loss of the STAT3-mediated cell cycle progression, antiapoptosis, and bcl-2 expression. We also identified valosine-containing protein (VCP) as a target gene for the Pim-1-mediated signal. Expression of a mutant VCP led cells to undergo apoptosis. These results indicate that Pim-family proteins play crucial roles in gp130-mediated cell proliferation and explain the synergy between Pim and c-Myc proteins in cell proliferation and lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis*
  • B-Lymphocytes / cytology
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / physiology*
  • Proto-Oncogene Proteins c-pim-1
  • STAT3 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • Valosin Containing Protein

Substances

  • Antigens, CD
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Il6st protein, mouse
  • Membrane Glycoproteins
  • PIM2 protein, human
  • Pim2 protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Cytokine Receptor gp130
  • PIM1 protein, human
  • Pim1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein
  • Vcp protein, mouse