IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

Oncogene. 1999 Jul 22;18(29):4191-9. doi: 10.1038/sj.onc.1202796.


Activation of the Jak/STAT pathway by cytokines has been shown to regulate differentiation, proliferation or apoptosis in hematopoeitic cells. Among the Stat proteins, STAT5 is activated by a broad range of cytokines. In order to study the role of STAT5 in hematopoietic cells, we stably expressed a dominant negative form of STAT5 (STAT5A delta749) in the IL-3 dependent bone marrow derived Ba/F3 cell line. Ba/F3 cells expressing STAT5A delta749 were found to be more sensitive to apoptosis than parental or control Ba/F3 cells after IL-3 withdrawal. Analysis of the expression of the cell death regulators, Bcl-2 and Bcl-x, revealed that the level of Bcl-x was lower in Ba/F3 cells expressing STAT5A delta749 than in control cells. IL-3 regulation of Bcl-x expression at protein and mRNA levels was impaired in these cells while that of Bcl-2 expression was unaffected. We further demonstrated that the Bcl-x gene promoter contained a proximal STAT consensus sequence that bound STAT5. Transactivation of a Bcl-x gene promoter reporter construct by STAT5 was observed in Ba/F3 cells. Introduction of a mutation in the STAT binding site abolished this transactivation. These data indicate that Bcl-x is probably a STAT5 target gene. They also support the involvement of STAT5 in hematopoietic cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects*
  • Genes, Dominant
  • Genes, Reporter
  • Genes, bcl-2
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Interleukin-3 / pharmacology*
  • Mice
  • Milk Proteins*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Recombinant Fusion Proteins / physiology
  • STAT5 Transcription Factor
  • Sequence Deletion
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription, Genetic
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • DNA-Binding Proteins
  • Interleukin-3
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Trans-Activators
  • bcl-X Protein