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Updated: Jan 26, 2026
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Modulation of the cell cycle regulating transcription factor E2F1 pathway by the proteasome following amino acid
Bertrand Fabre1, Ido Livneh1, Tamar Ziv2
1Technion Integrated Cancer Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, 3109601, Israel.
Abstract:
The proteasome is one of the main catalytic machineries of eukaryotic cells responsible for protein degradation, and is known to be regulated during several cellular stress conditions. Recent studies suggest that the activity of the proteasome is modulated following mTOR inhibition. However, it is not clear how this process affects the proteome. In the present study, we investigated the role of the proteasome in the modulation of the proteome of HeLa cells following amino acid starvation, a stress known to inhibit mTOR activity. We used label-free quantitative proteomics to identify proteins regulated by the proteasome in starved cells. We found that nearly 50% of the proteins the level of which decreased significantly during starvation stress, could be rescued by addition of the proteasome inhibitor MG132. This suggests a key role for the proteasome in reshaping the proteome under starvation. Importantly, the expression of several of these proteins is known to be dependent on the transcription factor E2F1. Further investigation of E2F1 level showed that this transcription factor along with several other proteins involved in its pathway are regulated by the proteasome upon amino acids starvation.
Insights
The proteasome plays a key role in reshaping the proteome during amino acid starvation stress by degrading specific proteins. Inhibiting the proteasome rescues nearly half of the proteins that decrease during starvation.
Area of Science:
- Cellular Biology
- Molecular Biology
- Proteomics
Background:
- The proteasome is a crucial cellular machine for protein degradation, its activity is regulated by cellular stress and mTOR inhibition.
- The precise impact of proteasome modulation on the overall proteome under stress, particularly amino acid starvation, remains unclear.
Purpose of the Study:
- To investigate the proteasome's role in modulating the proteome of HeLa cells during amino acid starvation.
- To identify proteins regulated by the proteasome under starvation-induced mTOR inhibition.
Main Methods:
- Label-free quantitative proteomics was employed to analyze protein expression changes.
- The proteasome inhibitor MG132 was used to assess the proteasome's contribution to protein level changes.
Main Results:
- Nearly 50% of proteins significantly decreased during starvation were rescued by proteasome inhibition (MG132).
- The proteasome is critical for proteome remodeling under amino acid starvation.
- Proteasome-mediated regulation was observed for the transcription factor E2F1 and its associated pathway proteins.
Conclusions:
- The proteasome actively reshapes the cellular proteome in response to amino acid starvation.
- Proteasome activity influences the expression of key regulatory proteins like E2F1 during cellular stress.
- These findings highlight the proteasome as a significant regulator of cellular adaptation to nutrient deprivation.
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