1] The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.
EMBO Rep. 2013 Nov;14(11):992-8. doi: 10.1038/embor.2013.152. Epub 2013 Sep 24.
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.
BH3 仅蛋白 Bim 是造血细胞凋亡的关键启动子。Bim 响应生长因子撤出而上调，体外研究表明转录因子 Foxo3a 是关键诱导因子。为了在体内检验这种调控的重要性，我们生成了 Bim 启动子内突变 Foxo 结合位点的小鼠（Bim(ΔFoxo/ΔFoxo)）。与 Bim 缺陷小鼠相反，Bim(ΔFoxo/ΔFoxo)小鼠具有正常的造血系统。此外，来自 Bim(ΔFoxo/ΔFoxo)和 wt 小鼠的细胞因子依赖性造血细胞以相似的速率死亡。这些结果表明，Foxo 转录因子对 Bim 的调控对于造血细胞的杀伤并不关键。
