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PMID: 12704079 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Translational control of SCL-isoform expression in hematopoietic lineage choice.

Genes & development ·Vol. 17 ·No. 8 ·2003-04-15 ·Pages 959-64

Calkhoven CF, Muller C, Martin R, Krosl G, Pietsch H, Hoang T, Leutz A

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.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Blotting, Northern Blotting, Western Bone Marrow/microbiology,pathology COS Cells Cell Differentiation Cell Lineage/genetics Colony-Forming Units Assay Cricetinae DNA Primers/chemistry DNA-Binding Proteins/genetics,metabolism Erythroid Precursor Cells/metabolism Eukaryotic Initiation Factor-2/metabolism Eukaryotic Initiation Factor-4E/metabolism Flow Cytometry Helix-Loop-Helix Motifs/genetics Hematopoietic System/physiology Humans Megakaryocytes/metabolism,pathology Open Reading Frames Peptide Initiation Factors/metabolism Polymerase Chain Reaction Protein Biosynthesis Protein Isoforms Protein Processing, Post-Translational Proto-Oncogene Proteins/genetics,metabolism Sequence Deletion Signal Transduction T-Cell Acute Lymphocytic Leukemia Protein 1 Transcription Factors/genetics,metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors DNA Primers DNA-Binding Proteins Eukaryotic Initiation Factor-2 Eukaryotic Initiation Factor-4E Peptide Initiation Factors Protein Isoforms Proto-Oncogene Proteins T-Cell Acute Lymphocytic Leukemia Protein 1 Transcription Factors TAL1 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Calkhoven Cornelis F
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Muller Christine
Martin Richard
Krosl Goradz
Pietsch Hubertus
Hoang Trang
Leutz Achim
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.251903
Published
2003-04-15
Pages
959-64
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196037
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1101/gad.251903 PMC Full Text View journal details
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