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Foxo-mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3-only protein.

ABSTRACT: The BH3-only protein Bim is a critical initiator of apoptosis in hematopoietic cells. Bim is upregulated in response to growth factor withdrawal and in vitro studies have implicated the transcription factor Foxo3a as a critical inducer. To test the importance of this regulation in vivo, we generated mice with mutated Foxo-binding sites within the Bim promoters (Bim(?Foxo/?Foxo)). Contrary to Bim-deficient mice, Bim(?Foxo/?Foxo) mice had a normal hematopoietic system. Moreover, cytokine-dependent haematopoietic cells from Bim(?Foxo/?Foxo) and wt mice died at similar rates. These results indicate that regulation of Bim by Foxo transcription factors is not critical for the killing of hematopoietic cells.

SUBMITTER: Herold MJ

PROVIDER: S-EPMC3818073 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Foxo-mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3-only protein.

Herold Marco J MJ Rohrbeck Leona L Lang Mathias J MJ Grumont Raelene R Gerondakis Steve S Tai Lin L Bouillet Philippe P Kaufmann Thomas T Strasser Andreas A

EMBO reports 20130924 11

The BH3-only protein Bim is a critical initiator of apoptosis in hematopoietic cells. Bim is upregulated in response to growth factor withdrawal and in vitro studies have implicated the transcription factor Foxo3a as a critical inducer. To test the importance of this regulation in vivo, we generated mice with mutated Foxo-binding sites within the Bim promoters (Bim(ΔFoxo/ΔFoxo)). Contrary to Bim-deficient mice, Bim(ΔFoxo/ΔFoxo) mice had a normal hematopoietic system. Moreover, cytokine-dependent ...[more]

PMID: 24060902

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