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

Abstract : 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.
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https://hal-univ-tours.archives-ouvertes.fr/hal-02425313
Contributor : Valérie Gouilleux <>
Submitted on : Monday, December 30, 2019 - 12:02:59 PM
Last modification on : Friday, January 10, 2020 - 4:12:18 PM

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S Dumon, S Constantino Rosa Santos, F Debierre-Grockiego, V Gouilleux-Gruart, L Cocault, et al.. IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line. Oncogene, Nature Publishing Group, 1999, 18 (29), pp.4191-4199. ⟨10.1038/sj.onc.1202796⟩. ⟨hal-02425313⟩

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