Translational control of SCL-isoform expression in hematopoietic lineage choice

被引：60

作者：

Calkhoven, CF

Müller, C

Martin, R

Krosl, G

Hoang, T

Leutz, A ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, Berlin, Germany

[2] Clin Res Inst Montreal, Hemopoiesis & Leukemia Lab, Montreal, PQ H2W 1R7, Canada

来源：

GENES & DEVELOPMENT | 2003年 / 17卷 / 08期

关键词：

hematopoiesis; lineage commitment; translation initiation; uORF; eIF4E; eIF2; alpha;

D O I：

10.1101/gad.251903

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We investigated the translational regulation of SCL protein expression and its role in hematopoietic lineage choice. We show that the expression of different SCL protein isoforms is regulated by signal transduction pathways that modulate translation initiation factor (eIF) function. A conserved small upstream open reading frame (uORF) in SCL transcripts acts as a cis-regulatory element for isoform expression. At the onset of erythroid differentiation, truncated SCL protein isoforms arise by alternative translation initiation and favor the erythroid lineage. in comparison, full-length SCL proteins are more efficient at enhancing the megakaryocyte lineage. Together, our studies unravel translational control as a novel mechanism regulating hematopoietic outcome.

引用

页码：959 / 964

页数：6

共 28 条

[1] Depletion of intracellular Ca2+ stores, phosphorylation of eIF2α, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole [J].