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(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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / deficiency
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Apoptosis Regulatory Proteins / genetics*
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Apoptosis Regulatory Proteins / metabolism
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Apoptosis* / drug effects
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Apoptosis* / genetics
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Base Sequence
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Bcl-2-Like Protein 11
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Binding Sites
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Carcinogenesis / metabolism
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Carcinogenesis / pathology
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Cell Death / drug effects
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Cytokines / pharmacology
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Forkhead Box Protein O3
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Forkhead Transcription Factors / deficiency
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Forkhead Transcription Factors / metabolism*
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HEK293 Cells
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Hematopoiesis / drug effects
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Hematopoietic System / cytology*
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Hematopoietic System / drug effects
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Hematopoietic System / metabolism
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Humans
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Lymphoma / pathology
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Membrane Proteins / deficiency
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Mice
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Molecular Sequence Data
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Mutation / genetics
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Promoter Regions, Genetic / genetics
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Protein Binding / drug effects
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Protein Binding / genetics
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-myc / metabolism
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Thymocytes / cytology
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Thymocytes / drug effects
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Thymocytes / metabolism
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Transcription, Genetic* / drug effects
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Cytokines
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Forkhead Box Protein O3
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Forkhead Transcription Factors
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FoxO3 protein, mouse
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-myc