Shirihai O S, Gregory T, Yu C, Orkin S H, Weiss M J
Division of Hematology and Oncology, Children's Hospital and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
EMBO J. 2000 Jun 1;19(11):2492-502. doi: 10.1093/emboj/19.11.2492.
Transcription factor GATA-1 is essential for normal erythropoiesis. GATA-binding sites are consistently found in promoters or enhancers of genes expressed selectively in erythroid cells. To discover novel GATA-1-regulated genes, we searched for GATA-1-activated transcripts in G1E cells, an erythroid line derived from GATA-1(-) embryonic stem cells. By subtractive analysis, we identified a new ATP-binding cassette (ABC) transporter that is strongly and rapidly induced by GATA-1. This protein, named ABC-me (for ABC-mitochondrial erythroid), localizes to the mitochondrial inner membrane and is expressed at particularly high levels in erythroid tissues of embryos and adults. ABC-me is induced during erythroid maturation in cell lines and primary hematopoietic cells, and its overexpression enhances hemoglobin synthesis in erythroleukemia cells. The ABC proteins participate in diverse physiological processes by coupling ATP hydrolysis to the transport of a variety of substrates across cell membranes. We speculate that ABC-me, a newly identified erythroid-expressed ABC superfamily member, may mediate critical mitochondrial transport functions related to heme biosynthesis.
转录因子GATA-1对正常红细胞生成至关重要。在红系细胞中选择性表达的基因的启动子或增强子中始终能发现GATA结合位点。为了发现新的GATA-1调控基因,我们在G1E细胞中寻找GATA-1激活的转录本,G1E细胞是一种源自GATA-1(-)胚胎干细胞的红系细胞系。通过消减分析,我们鉴定出一种新的ATP结合盒(ABC)转运蛋白,它能被GATA-1强烈且快速地诱导。这种蛋白名为ABC-me(ABC-线粒体红系),定位于线粒体内膜,在胚胎和成年动物的红系组织中表达水平特别高。ABC-me在细胞系和原代造血细胞的红系成熟过程中被诱导,其过表达增强了红白血病细胞中的血红蛋白合成。ABC蛋白通过将ATP水解与多种底物跨细胞膜的转运偶联,参与多种生理过程。我们推测,ABC-me作为新鉴定出的红系表达的ABC超家族成员,可能介导与血红素生物合成相关的关键线粒体转运功能。