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Updated: Jul 10, 2026
10:56
Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
Published on: May 17, 2014
Translational control of C/EBPalpha and C/EBPbeta isoform expression
C F Calkhoven1, C Müller, A Leutz
1Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany. calkhov@mdc-berlin.de
Genes & Development
|August 2, 2000
Summary
The ratio of CCAAT/enhancer binding protein (C/EBP) isoforms, controlled by PKR and mTOR signaling, dictates cell fate. Aberrant expression disrupts differentiation and induces a transformed phenotype.
Area of Science:
- Molecular Biology
- Cell Biology
- Gene Regulation
Background:
- CCAAT/enhancer binding protein (C/EBP) transcription factors regulate cell differentiation and proliferation.
- Different C/EBP isoforms, generated by differential translation initiation from C/EBPalpha and C/EBPbeta mRNAs, possess distinct functions.
- These isoforms differ in their N-terminal regions, impacting gene regulation and proliferation control.
Purpose of the Study:
- To investigate the signaling pathways controlling the ratio of C/EBP isoform expression.
- To elucidate the role of eukaryotic translation initiation factors in C/EBP isoform regulation.
- To determine the impact of aberrant C/EBP isoform expression on cell fate and differentiation.
Main Methods:
- Analysis of PKR and mTOR signaling pathways.
- Investigation of eukaryotic translation initiation factors eIF-2alpha and eIF-4E.
- Study of conserved upstream open reading frames in C/EBPalpha and C/EBPbeta mRNAs.
- Assessment of C/EBP isoform expression in 3T3-L1 cells.
Main Results:
- PKR and mTOR signaling pathways regulate C/EBP isoform ratios via eIF-2alpha and eIF-4E, respectively.
- A conserved upstream open reading frame in C/EBP mRNAs is essential for regulated translation initiation.
- Deregulated or ectopic expression of C/EBP isoforms disrupts terminal differentiation and induces a transformed phenotype in 3T3-L1 cells.
Conclusions:
- The translational control of C/EBPalpha and C/EBPbeta isoform expression is critical for determining cell fate.
- Aberrant C/EBP isoform expression patterns can lead to loss of differentiation and cellular transformation.
- Understanding C/EBP translational regulation offers insights into cell differentiation and disease processes.
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