ArticlePloS one2014
Proteasome inhibitors alter levels of intracellular peptides in HEK293T and SH-SY5Y cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Limitations of Mass Spectrometry-Based Peptidomic Approaches.Journal of the American Society for Mass Spectrometry · 2015Pooled it
- Pep19: A Novel Approach for Reducing Visceral Fat and Improving Sleep Quality in Obese Adults-Results From an Early-Stage Clinical Trial.Diabetes/metabolism research and reviews · 2025Trial
- Peptidomics of Zebrafish Brain in a 6-OHDA-Induced Neurodegeneration Model.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Methods for Intracellular Peptidomic Analysis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Quantitative Peptidomics: General Considerations.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Quantitative Peptidomics Using Reductive Methylation of Amines.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Origins, Technological Advancement, and Applications of Peptidomics.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Neurolysin Knockout Mice in a Diet-Induced Obesity Model.International journal of molecular sciences · 2023Article
- Proteasomal Stimulation by MK886 and Its Derivatives Can Rescue Tau-Induced Neurite Pathology.Molecular neurobiology · 2023Article
- Revealing Natural Intracellular Peptides in Gills of SeahorseBiomolecules · 2023Article
- Isolation of Proteasome-Trapped Peptides (PTPs) for Degradome Analysis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Epoxomicin, a Selective Proteasome Inhibitor, Activates AIM2 Inflammasome in Human Retinal Pigment Epithelium Cells.Antioxidants (Basel, Switzerland) · 2022Article
- The role of cellular proteostasis in antitumor immunity.The Journal of biological chemistry · 2022Review
- Effect of FKBP12-Derived Intracellular Peptides on Rapamycin-Induced FKBP-FRB Interaction and Autophagy.Cells · 2022Article
- New Intracellular Peptide Derived from Hemoglobin Alpha Chain Induces Glucose Uptake and Reduces Blood Glycemia.Pharmaceutics · 2021Article
- Peptidome: Chaos or Inevitability.International journal of molecular sciences · 2021Review
- The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.Nature communications · 2021Article
- Article
- Structural Insights into Substrate Recognition and Processing by the 20S Proteasome.Biomolecules · 2021Review
- Insights into the Molecular Basis of Genome Stability and Pristine Proteostasis in Naked Mole-Rats.Advances in experimental medicine and biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell.
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Registered trials
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