ArticleeLife2015
Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Targeting USP14 sensitizes glioma to radiotherapy through exacerbated reactive oxygen species accumulation.Medical gas research · 2027Article
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- USP14 promotes epithelial-mesenchymal transition and functions as a multifaceted biomarker in lung adenocarcinoma.Discover oncology · 2026Article
- Identification of AKOS, a Chikungunya virus inhibitor, as a USP14 inhibitor for colorectal cancer treatment.Acta pharmacologica Sinica · 2025Article
- Anti-Atrophic Effects of Dichotomine B fromMolecules (Basel, Switzerland) · 2025Article
- USP14 Mediates Molecular Mechanisms Regulating Aortic Valve Stenosis Through Ubiquitination.Journal of cellular and molecular medicine · 2025Article
- Activation of the 20S proteasome core particle prevents cell death induced by oxygen- and glucose deprivation in cultured cortical neurons.Apoptosis : an international journal on programmed cell death · 2025Article
- Dynamic networks connect the USP14 active site region with the proteasome interaction surface.Protein science : a publication of the Protein Society · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- 4-Octyl Itaconate Alleviates Myocardial Ischemia-Reperfusion Injury Through Promoting Angiogenesis via ERK Signaling Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- USP14 is crucial for proteostasis regulation and α-synuclein degradation in human SH-SY5Y dopaminergic cells.Heliyon · 2025Article
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- Artesunate disrupts germ layer formation by inhibiting BMP signaling pathway.Animal cells and systems · 2025Article
- The effect of AKT inhibition in α-synuclein-dependent neurodegeneration.Frontiers in molecular neuroscience · 2025Article
- Stress on the Endoplasmic Reticulum Impairs the Photosynthetic Efficiency of Chlamydomonas.International journal of molecular sciences · 2024Article
- Article
- Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression.Cell death & disease · 2024Article
- PKCiota Inhibits the Ferroptosis of Esophageal Cancer Cells via Suppressing USP14-Mediated Autophagic Degradation of GPX4.Antioxidants (Basel, Switzerland) · 2024Article
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Regulation of ubiquitin-proteasome system (UPS), which controls the turnover of short-lived proteins in eukaryotic cells, is critical in maintaining cellular proteostasis. Here we show that USP14, a major deubiquitinating enzyme that regulates the UPS, is a substrate of Akt, a serine/threonine-specific protein kinase critical in mediating intracellular signaling transducer for growth factors. We report that Akt-mediated phosphorylation of USP14 at Ser432, which normally blocks its catalytic site in the inactive conformation, activates its deubiquitinating activity in vitro and in cells. We also demonstrate that phosphorylation of USP14 is critical for Akt to regulate proteasome activity and consequently global protein degradation. Since Akt can be activated by a wide range of growth factors and is under negative control by phosphoinosotide phosphatase PTEN, we suggest that regulation of UPS by Akt-mediated phosphorylation of USP14 may provide a common mechanism for growth factors to control global proteostasis and for promoting tumorigenesis in PTEN-negative cancer cells.
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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.