ArticleNature communications2017
Identifying the ubiquitination targets of E6AP by orthogonal ubiquitin transfer.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- Cell-type-specific dysregulated gene expression in the frontal cortex of an Angelman syndrome pig model.Human molecular genetics · 2026Article
- Members of the RhoA subfamily of GTPases suppress the stimulatory effect of the HPV E6 oncoprotein on the ubiquitin ligase E6AP.Scientific reports · 2026Article
- Dual Pathways of UBE4B Inhibit Apoptosis in p53-Positive Tumor Cells via CCAR2 Degradation.International journal of molecular sciences · 2026Article
- Engineering an orthogonal ubiquitin transfer cascade with RING E3 RNF38 by phage display to reveal its regulation of nuclear transport.The Journal of biological chemistry · 2026Article
- UBE4B Mediates Mitophagy via NIPSNAP1 Ubiquitination and NDP52 Recruitment.International journal of molecular sciences · 2026Article
- UBE3A promotes foam cell formation and counters remyelination by targeting ABCA1 for proteasomal degradation.Nature communications · 2025Article
- Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.iScience · 2025Article
- The E3 Ligase NEDD4L Prevents Colorectal Cancer Liver Metastasis via Degradation of PRMT5 to Inhibit the AKT/mTOR Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.Structure (London, England : 1993) · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- SelK promotes glioblastoma cell proliferation by inhibiting β-TrCP1 mediated ubiquitin-dependent degradation of CDK4.Journal of experimental & clinical cancer research : CR · 2024Article
- A ubiquitin-specific, proximity-based labeling approach for the identification of ubiquitin ligase substrates.Science advances · 2024Article
- CDKL3 is a targetable regulator of cell cycle progression in cancers.The Journal of clinical investigation · 2024Article
- PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia.Autophagy · 2024Article
- The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons.bioRxiv : the preprint server for biology · 2023Article
- Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Effects of UBE3A on Cell and Liver Metabolism through the Ubiquitination of PDHA1 and ACAT1.Biochemistry · 2023Article
- Ubiquitin proteasome system in immune regulation and therapeutics.Current opinion in pharmacology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
E3 ubiquitin (UB) ligases are the ending modules of the E1-E2-E3 cascades that transfer UB to cellular proteins and regulate their biological functions. Identifying the substrates of an E3 holds the key to elucidate its role in cell regulation. Here, we construct an orthogonal UB transfer (OUT) cascade to identify the substrates of E6AP, a HECT E3 also known as Ube3a that is implicated in cancer and neurodevelopmental disorders. We use yeast cell surface display to engineer E6AP to exclusively transfer an affinity-tagged UB variant (xUB) to its substrate proteins. Proteomic identification of xUB-conjugated proteins in HEK293 cells affords 130 potential E6AP targets. Among them, we verify that MAPK1, CDK1, CDK4, PRMT5, β-catenin, and UbxD8 are directly ubiquitinated by E6AP in vitro and in the cell. Our work establishes OUT as an efficient platform to profile E3 substrates and reveal the cellular circuits mediated by the E3 enzymes.
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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.