GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression
GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression
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DOI：
10.1182/blood.v94.1.87.413k41_87_96
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发表时间：
1999-07-01
期刊：
影响因子：
20.3
通讯作者：
Weiss, MJ
中科院分区：
文献类型：
--
作者：
Gregory, T;Yu, CN;Weiss, MJ
转录因子GATA-1对于正常的红细胞生成是必不可少的，通过检查体外分化的胚胎干细胞，我们以前表明，在没有GATA-1的情况下，承诺的红斑前体未能完全成熟，而是经历了凋亡。 GATA-1控制细胞存活的机制尚不清楚。在这里，我们报告说，在红细胞细胞中，GATA-1强烈诱导抗凋亡蛋白BCl-X（L）的表达，但不相关的蛋白质Bcl-2和Mcl-1。与Bcl-X（L）在介导GATA-1诱导的红细胞生存中的作用一致，体外分化的Bcl-X（L）（ - - ）胚胎干细胞无法产生可行的成熟的定性红细胞，A表型类似于GATA-1基因破坏的表型，此外，我们证明了促红细胞生成素，这也是红红色所需的细胞存活，与GATA-1合作以刺激BCL-X（L）基因表达并在末期成熟过程中维持红细胞细胞活力。总之，我们的数据表明，BCL-X（L）对于正常的红细胞发育至关重要，并提出了一个调节层次结构，其中BCl-X（L）是GATA-1和促红细胞生成素介导的信号的关键下游效应子。 （c）1999年美国血液学学会。
The transcription factor GATA-1 is essential for normal erythropoiesis, By examining in vitro-differentiated embryonic stem cells, we showed previously that in the absence of GATA-1, committed erythroid precursors fail to complete maturation and instead undergo apoptosis. The mechanisms by which GATA-1 controls cell survival are unknown. Here we report that in erythroid cells, GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-x(L), but not the related proteins bcl-2 and mcl-1. Consistent with a role for bcl-x(L) in mediating GATA-1-induced erythroid cell survival, in vitro-differentiated bcl-x(L)(-/-) embryonic stem cells fail to generate viable mature definitive erythroid cells, a phenotype resembling that of GATA-1 gene disruption, In addition, we show that erythropoietin, which is also required for erythroid cell survival, cooperates with GATA-1 to stimulate bcl-x(L) gene expression and to maintain erythroid cell viability during terminal maturation. Together, our data show that bcl-x(L) is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-x(L) is a critical downstream effector of GATA-1 and erythropoietin-mediated signals. (C) 1999 by The American Society of Hematology.