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Updated: May 10, 2026
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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
A putative stimulatory role for activator turnover in gene expression
J Russell Lipford1, Geoffrey T Smith, Yong Chi
1Howard Hughes Medical Institute, Division of Biology, MC 156-29, California Institute of Technology, 1200 E. California Boulevard, Pasadena, California 91125, USA.
Nature
|November 4, 2005
Summary
The ubiquitin-proteasome system (UPS) degrades transcriptional activators, but this proteolysis can paradoxically enhance gene expression. Inhibiting the proteasome impairs the function of key yeast activators like Gcn4.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The ubiquitin-proteasome system (UPS) regulates protein levels and influences cellular processes.
- Transcriptional activators are key determinants of gene expression.
- The UPS's role in transcriptional regulation is complex, with emerging evidence for non-proteolytic functions.
Purpose of the Study:
- To investigate the role of UPS-dependent proteolysis in stimulating the function of inducible transcriptional activators.
- To determine if proteolysis of specific activators enhances their transcriptional activity.
Main Methods:
- Utilized yeast models to study the function of transcriptional activators Gcn4, Gal4, and Ino2/4.
- Employed proteasome inhibition and specific mutations in ubiquitin ligases (SCF(Cdc4)) and ubiquitin.
- Assessed the impact on target gene transcription and RNA polymerase II association.
Main Results:
- Proteasome inhibition reduced transcription of targets for Gcn4, Gal4, and Ino2/4.
- Mutations affecting Gcn4 ubiquitination and degradation impaired target gene transcription.
- Transcriptional defects occurred despite increased Gcn4 abundance, and RNA polymerase II association decreased.
Conclusions:
- Proteolysis of certain transcriptional activators by the UPS can stimulate their function.
- UPS-dependent degradation is crucial for the proper activity of inducible transcriptional activators in yeast.
- Targeted degradation, rather than mere abundance, is critical for activator function.
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