Translational control of SCL-isoform expression in hematopoietic lineage choice

Cornelis F Calkhoven, Christine Muller, Richard Martin, Goradz Krosl, Hubertus Pietsch, Trang Hoang, Achim Leutz

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54 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)959-64
Number of pages6
JournalGenes & Development
Volume17
Issue number8
DOIs
Publication statusPublished - 15-Apr-2003
Externally publishedYes

Keywords

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Northern
  • Blotting, Western
  • Bone Marrow
  • COS Cells
  • Cell Differentiation
  • Cell Lineage
  • Colony-Forming Units Assay
  • Cricetinae
  • DNA Primers
  • DNA-Binding Proteins
  • Erythroid Precursor Cells
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4E
  • Flow Cytometry
  • Helix-Loop-Helix Motifs
  • Hematopoietic System
  • Humans
  • Megakaryocytes
  • Open Reading Frames
  • Peptide Initiation Factors
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Protein Isoforms
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins
  • Sequence Deletion
  • Signal Transduction
  • Transcription Factors

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