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

• Published in: Oncogene Vol. 18; no. 29; pp. 4191 - 4199
• Main Authors: DUMON, S, ROSA SANTOS, S. C, DEBIERRE-GROCKIEGO, F, GOUILLEUX-GRUART, V, COCAULT, L, BOUCHERON, C, MOLLAT, P, GISSELBRECHT, S, GOUILLEUX, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 22.07.1999; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Ageing, cell death; Animals; Apoptosis; Bcl-2 protein; Bcl-x protein; Binding sites; Biological and medical sciences; Bone marrow; Cell activation; Cell death; Cell Line; Cell physiology; Cell proliferation; Cell survival; Conserved sequence; Cytokines; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation - drug effects; Genes, bcl-2; Genes, Dominant; Genes, Reporter; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Interleukin 3; Interleukin-3 - pharmacology; Life Sciences; Mice; Milk Proteins; Molecular and cellular biology; Promoter Regions, Genetic; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Recombinant Fusion Proteins - physiology; Sequence Deletion; Stat5 protein; STAT5 Transcription Factor; Trans-Activators - genetics; Trans-Activators - physiology; Transcription, Genetic; Signal transduction; Vertebrata; Regulation(control); Cell line; Mammalia; Gene; Interleukin 3; Cytokine; Hematopoietic cell; Bone marrow; Gene expression; Apoptosis
• ISSN: 0950-9232; 1476-5594
• 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.