ArticleThe Journal of biological chemistry2012
The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- A Balanced Inversion Polymorphism Exhibits a Dominance Reversal at the Gene Expression Level that Depends on Developmental Context.Molecular biology and evolution · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Ubiquitin-specific protease: an emerging key player in cardiomyopathy.Cell communication and signaling : CCS · 2025Review
- USP12 facilitates gastric cancer progression via stabilizing YAP.Cell death discovery · 2024Article
- In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases.Frontiers in molecular biosciences · 2024Review
- The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.Nature communications · 2023Article
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
- USP12 promotes antiviral responses by deubiquitinating and stabilizing IFI16.PLoS pathogens · 2023Article
- Ubiquitin-modifying enzymes in Huntington's disease.Frontiers in molecular biosciences · 2023Review
- Deubiquitinating Enzyme USP12 Regulates the Pro-Apoptosis Protein Bax.International journal of molecular sciences · 2022Article
- Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1.Oncogene · 2022Article
- USP12 downregulation orchestrates a protumourigenic microenvironment and enhances lung tumour resistance to PD-1 blockade.Nature communications · 2021Article
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- Review
- The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation.The Journal of biological chemistry · 2020Article
- NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain.Journal of molecular cell biology · 2020Article
- Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics.Trends in biochemical sciences · 2020Review
- Deubiquitylation and stabilization of Notch1 intracellular domain by ubiquitin-specific protease 8 enhance tumorigenesis in breast cancer.Cell death and differentiation · 2020Article
- USP12 translocation maintains interferon antiviral efficacy by inhibiting CBP acetyltransferase activity.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling is critical for development and adult tissue physiology, controlling cell fate in a context-dependent manner. Upon ligand binding, the transmembrane Notch receptor undergoes two ordered proteolytic cleavages releasing Notch intracellular domain, which regulates the transcription of Notch target genes. The strength of Notch signaling is of crucial importance and depends notably on the quantity of Notch receptor at the cell surface. Using an shRNA library screen monitoring Notch trafficking and degradation in the absence of ligand, we identified mammalian USP12 and its Drosophila melanogaster homolog as novel negative regulators of Notch signaling. USP12 silencing specifically interrupts Notch trafficking to the lysosomes and, as a consequence, leads to an increased amount of receptor at the cell surface and to a higher Notch activity. At the biochemical level, USP12 with its activator UAF1 deubiquitinate the nonactivated form of Notch in cell culture and in vitro. These results characterize a new level of conserved regulation of Notch signaling by the ubiquitin system.
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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.