Enforced expression of the Mr 33,000 Pim-1 kinase enhances factor-independent survival and inhibits apoptosis in murine myeloid cells.
Expression of the Mr 33,000 human Pim-1 protein is induced in hematopoietic cells by a variety of growth factors and cytokines. We have introduced the human pim-1 cDNA via retroviral transduction into interleukin (IL)-3-dependent FDC-P1 cells and examined the resulting phenotype. Compared with cells infected with a neo-encoding retrovirus (FD/neo), cells infected with a pim-1-transducing virus (FD/hpim) showed longer survival or autonomous growth in suspension culture in the absence of IL-3, as well as IL-3-independent clonogenic growth in semisolid medium. The unique murine Mr 44,000 Pim-1 protein, as well as human proteins with short C- or N-terminal truncations, also was biologically active. This effect of Pim-1 expression was associated with a decrease in apoptotic cells and an increase in G0/G1-phase cells, and the increase in G0/G1-phase cells caused by enforced expression of Pim-1 was due to a decrease in apoptosis rather than to a decrease in transit of the G1-S-phase checkpoint. The Pim-1 kinase appears to function primarily as a survival factor in factor-dependent FDCP-1 cells subjected to either cytokine withdrawal or exposure to cytotoxic agents.
Lilly
M
M
Department of Medicine, University of Washington and Veterans Affairs Medical Center, Seattle 98108, USA.
Kraft
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D051573:Proto-Oncogene Proteins c-pim-1; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D013997:Time Factors; D014162:Transfection
D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C496634:PIM1 protein, human; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1