Pim-1 kinase protects hematopoietic FDC cells from genotoxin-induced death.

Academic Article

Abstract

  • The hematopoietic cell S/T kinase Pim-1 was originally discovered as a target of murine leukemia provirus integration, and when expressed at increased levels is predisposing to lymphomagenesis. Recently, Pim-1 has been shown to enhance the activities of p100, c-Myb and cdc25a, and in part this might explain reported effects on mitogenesis. In the context of cytokine withdrawal, Pim-1 also can attenuate programmed cell death (PCD). Cytokine withdrawal, however, alters signaling pathways and can complicate the dissection of mitogenic vs apoptotic responses. To better study possible effects of Pim-1 on PCD, a hematopoietic cell model was developed in which proliferation was supported efficiently by SCF plus EPO in the absence of endogenous Pim-1 gene expression. This was provided by factor-dependent FDCW2 cells that express endogenous and functional c-Kit, and were transfected stably with truncated Epo receptor form mutated at a Y343 STAT5 binding site. In proliferating cells, exogenously expressed Pim-1 was observed to efficiently inhibit PCD as induced by either Co60 or adriamycin, and the dose-dependent nature of this effect was established in several independent clones. By comparison, effects of exogenous Pim-1 on mitogenesis were nominal. In addition, in cell fractionation studies an estimated 25% of Mr 34000 Pim-1 (but not Mr 44000 Pim-1) was present in nuclear extracts. Thus, Pim-1 efficiently buffers hematopoietic progenitor cells against death as induced by several clinically important apoptotic agents, and may directly target nuclear effectors.
  • Authors

  • Pircher, TJ
  • Zhao, S
  • Geiger, JN
  • Joneja, B
  • Wojchowski, Don
  • Status

    Publication Date

  • July 27, 2000
  • Published In

  • Oncogene  Journal
  • Keywords

  • Apoptosis
  • Cell Division
  • Cell Line
  • Cobalt
  • Doxorubicin
  • Gene Expression
  • Hematopoietic Stem Cells
  • Models, Biological
  • Mutagens
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-pim-1
  • Digital Object Identifier (doi)

    Pubmed Id

  • 10951575
  • Start Page

  • 3684
  • End Page

  • 3692
  • Volume

  • 19
  • Issue

  • 32