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

被引：26

作者：

Herold, Marco J. ^{[1
,2
]}

Rohrbeck, Leona ^{[1
,2
]}

Lang, Mathias J. ^{[1
,2
]}

Grumont, Raelene ^{[3
,4
]}

Gerondakis, Steve ^{[3
,4
]}

Tai, Lin ^{[1
,2
]}

Bouillet, Philippe ^{[1
,2
]}

Kaufmann, Thomas ^{[1
]}

Strasser, Andreas ^{[1
,2
]}

机构：

[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia

[3] Monash Univ, Australian Ctr Blood Dis, Melbourne, Vic 3004, Australia

[4] Monash Univ, Cent Clin Sch, Dept Clin Hematol, Melbourne, Vic 3004, Australia

来源：

EMBO REPORTS | 2013年 / 14卷 / 11期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

apoptosis; Bcl-2; BH3-only proteins; Bim; hematopoiesis; FAMILY-MEMBER BIM; BCL-2; FAMILY; LYMPHOCYTE DEVELOPMENT; DEATH; PUMA; EXPRESSION; SURVIVAL; DELETION; SHUTDOWN;

D O I：

10.1038/embor.2013.152

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：992 / 998

页数：7

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