Synergistic Roles for Pim-1 and c-Myc in STAT3-Mediated Cell Cycle Progression and Antiapoptosis

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....

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1999-12, Vol.11 (6), p.709-719
Main Authors: Shirogane, Takahiro, Fukada, Toshiyuki, Muller, Joyce M.M, Shima, David T, Hibi, Masahiko, Hirano, Toshio
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases
Animals
Antigens, CD - genetics
Antigens, CD - metabolism
Apoptosis
B-Lymphocytes - cytology
c-Myc protein
Cell Cycle - physiology
Cell Cycle Proteins - metabolism
Cell Line
Cytokine Receptor gp130
cytokine receptors
DNA-Binding Proteins - metabolism
glycoprotein gp130
Humans
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Pim-1 protein
Pim-2 protein
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
Signal Transduction
Stat3 protein
STAT3 Transcription Factor
Trans-Activators - metabolism
Tumor Cells, Cultured
Valosin Containing Protein
valosine-containing protein
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80145-4