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Insulin-Degrading Enzyme Regulates mRNA Processing and May Interact with the CCR4-NOT Complex
Barbara Bertocci1, Ayse Yilmaz1, Emmanuelle Waeckel-Énée1
1Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, F-75015 Paris, France.
Cells
|June 11, 2025
Summary
Insulin-degrading enzyme (Ide) interacts with the CCR4-NOT complex, suggesting a role beyond insulin degradation. This finding reveals Ide
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Physiology
Background:
- Insulin-degrading enzyme (Ide) is a metalloprotease.
- Its broader role in protein homeostasis is not fully understood.
- Ide is upregulated in stress situations.
Purpose of the Study:
- To investigate the broader role of Ide in protein homeostasis.
- To identify novel Ide functions using proteomics and transcriptomics.
- To explore Ide interactions in pancreatic islet cells.
Main Methods:
- Proteomics and transcriptomics analysis of Ide knockout and wild-type pancreatic islet cells.
- Single-cell transcriptome analysis.
- Proximity biotinylation to examine the interactome of human cytosolic Ide.
Main Results:
- Upregulation of RNA processing, translation, and splicing pathways in Ide+/+ cells compared to Ide-/- cells.
- Identification of Ide interaction with subunits of the CCR4-NOT complex.
- CCR4-NOT complex identified as a key mRNA deadenylase.
Conclusions:
- Ide may cooperate with the CCR4-NOT complex to regulate gene expression.
- This cooperation could involve both Ide's protease and CCR4-NOT's deadenylase functions.
- A novel model for Ide's role in protein expression during stress is proposed.
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