ArticleCellular and molecular life sciences : CMLS2018
The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S.
Article in Cellular and molecular life sciences : CMLS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Tetra-anionic porphyrin mimics protein-protein interactions between regulatory particles and the catalytic core, allosterically activating human 20S proteasome.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Navigation Between Alzheimer's Disease (AD) and Its Various Pathophysiological Trajectories: The Pathogenic Link to Neuroimmunology-Genetics and Neuroinflammation.International journal of molecular sciences · 2025Review
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Insulin-Degrading Enzyme Regulates mRNA Processing and May Interact with the CCR4-NOT Complex.Cells · 2025Article
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- Insulin-degrading enzyme regulates insulin-directed cellular autoimmunity in murine type 1 diabetes.Frontiers in immunology · 2024Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Association between polymorphism rs2421943 of the insulin-degrading enzyme and schizophrenia: Preliminary report.Journal of clinical laboratory analysis · 2023Article
- Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.Biomolecules · 2023Article
- Electronic Circular Dichroism Detects Conformational Changes Associated with Proteasome Gating Confirmed Using AFM Imaging.Biomolecules · 2023Article
- Comprehensive Analysis of Proteasomal Complexes in Mouse Brain Regions Detects ENO2 as a Potential Partner of the Proteasome in the Striatum.Cellular and molecular neurobiology · 2022Article
- New Insights on the Regulation of the Insulin-Degrading Enzyme: Role of microRNAs and RBPs.Cells · 2022Article
- A novel and atypical NF-KB pro-inflammatory program regulated by a CamKII-proteasome axis is involved in the early activation of Muller glia by high glucose.Cell & bioscience · 2022Article
- Proteasome complexes experience profound structural and functional rearrangements throughout mammalian spermatogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Insulin-Degrading Enzyme Is a Non Proteasomal Target of Carfilzomib and Affects the 20S Proteasome Inhibition by the Drug.Biomolecules · 2022Article
- The insulin-degrading enzyme as a link between insulin and neuropeptides metabolism.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Review
- Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE) ≤ 30 nM and activating at (IDE) ≥ 30 nM. Only an activating effect is observed in a yeast mutant locked in the "open" conformation (i.e., the α-3ΔN 20S), envisaging a possible role of IDE as modulator of the 20S "open"-"closed" allosteric equilibrium. Protein-protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S α-3 subunit which regulates the gate opening of the 20S.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.