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

Herold, Marco J.; Rohrbeck, Leona; Lang, Mathias J.; Grumont, Raelene; Gerondakis, Steve; Tai, Lin; Bouillet, Philippe; Kaufmann, Thomas; Strasser, Andreas (2013). Foxo-mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3-only protein. EMBO REPORTS, 14(11), pp. 992-998. Nature 10.1038/embor.2013.152

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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 haematopoietic cells from Bim(ΔFoxo/ΔFoxo) 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Kaufmann, Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1469-221X

Publisher:

Nature

Language:

English

Submitter:

Anita Dähler

Date Deposited:

06 Dec 2013 03:49

Last Modified:

10 Oct 2019 12:02

Publisher DOI:

10.1038/embor.2013.152

PubMed ID:

24060902

Uncontrolled Keywords:

apoptosis; Bcl-2; BH3-only proteins; Bim; hematopoiesis

BORIS DOI:

10.7892/boris.39538

URI:

https://boris.unibe.ch/id/eprint/39538

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