Foxo-mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3-only protein
Foxo-mediated Bim transcription is dispensable for the apoptosis of hematopoietic cells that is mediated by this BH3-only protein
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DOI：
10.1038/embor.2013.152
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发表时间：
2013-11-01
期刊：
影响因子：
7.7
通讯作者：
Strasser, Andreas
中科院分区：
文献类型：
--
作者：
Herold, Marco J.;Rohrbeck, Leona;Strasser, Andreas
BH 3-only蛋白Bim是造血细胞凋亡的关键起始物。Bim在生长因子撤除后上调，体外研究表明转录因子Foxo 3a是一个关键的诱导因子。为了测试这种调节在体内的重要性，我们产生了在Bim启动子内具有突变的Foxo结合位点的小鼠（Bim（Delta Foxo/Delta Foxo））。与Bim缺陷小鼠相反，Bim（Delta Foxo/Delta Foxo）小鼠具有正常的造血系统。此外，Bim（Delta Foxo/Delta Foxo）和野生型小鼠的精氨酸依赖性造血细胞死亡率相似。这些结果表明，Foxo转录因子对Bim的调节对于造血细胞的杀伤并不关键。
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(Delta Foxo/Delta Foxo)). Contrary to Bim-deficient mice, Bim(Delta Foxo/Delta Foxo) mice had a normal hematopoietic system. Moreover, cytokine-dependent haematopoietic cells from Bim(Delta Foxo/Delta 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.