ArticleInternational journal of molecular sciences2016
APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Ligand binding Pro-miscuity of acylpeptide hydrolase, structural analysis of a detoxifying serine hydrolase.Protein science : a publication of the Protein Society · 2025Article
- Acylamino acid-releasing enzyme, a bifunctional protease with a potential role in aging.Journal of experimental botany · 2025Review
- A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis.Communications biology · 2023Article
- A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase-meropenem complex.Chemical science · 2022Article
- Differential Distribution and Activity Profile of Acylpeptide Hydrolase in the Rat Seminiferous Epithelium.Biomedicines · 2022Article
- Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme.International journal of molecular sciences · 2021Article
- Approaches to inhibiting oncogenic K-Ras.Small GTPases · 2021Review
- Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target?Molecular biology reports · 2021Article
- Quantification of residual hydrophobic fusion peptide with monomer and dimer forms using reversed-phase liquid chromatography.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2020Article
- Acylpeptide hydrolase (APEH) sequence variants with potential impact on the metabolism of the antiepileptic drug valproic acid.Metabolic brain disease · 2019Article
- Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function.Journal of cell science · 2019Article
- Advances in autoimmune myasthenia gravis management.Expert review of neurotherapeutics · 2018Review
- Differential Proteome Analysis of Extracellular Vesicles from Breast Cancer Cell Lines by Chaperone Affinity Enrichment.Proteomes · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH-proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-κB, p21(Waf1), and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies.
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