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

Marco Herold, Leona Rohrbeck, Mathias Lang, Raelene Joy Grumont, Steven Demetrious Gerondakis, Lin Tai, Phillipe Bouillet, Thomas Kaufmann, Andreas Strasser

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21 Citations (Scopus)

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. ? 2013 European Molecular Biology Organization
Original languageEnglish
Pages (from-to)992 - 998
Number of pages7
JournalEMBO Reports
Volume14
Issue number11
DOIs
Publication statusPublished - 2013

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