ABC-me: a novel mitochondrial transporter induced by GATA-1 during erythroid differentiation

被引:127
作者
Shirihai, OS
Gregory, T
Yu, CN
Orkin, SH
Weiss, MJ
机构
[1] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
[3] Ontogeny Inc, Cambridge, MA 02138 USA
[4] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA
关键词
ABC transporter; erythropoiesis; GATA-1; hemoglobin; mitochondria;
D O I
10.1093/emboj/19.11.2492
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
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)under bar>-(m) under bar itochondrial (e) under bar rythroid), 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.
引用
收藏
页码:2492 / 2502
页数:11
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