ArticleMolecular and cellular biology1999
The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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Who cites it
171 citing papers in PubMed, 457 citations in OpenAlex.
- Cell-type-specific dysregulated gene expression in the frontal cortex of an Angelman syndrome pig model.Human molecular genetics · 2026Article
- A one-week automated genome-wide optical pooled screen using OttoSeq.Genome biology · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- UBE3A isoform-selective and non-selective contributions to Angelman syndrome phenotypes.Molecular psychiatry · 2026Article
- UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects.Molecular autism · 2025Article
- Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids.Communications biology · 2025Article
- A long journey to the discovery of nuclear receptor coactivator existence, physiology, pathology, and therapy.The Journal of biological chemistry · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- E6AP is essential for the proliferation of HPV-positive cancer cells by preventing senescence.PLoS pathogens · 2025Article
- Sex-biasing influence of autism-associatedScience advances · 2024Article
- The role of glia in the dysregulation of neuronal spinogenesis in Ube3a-dependent ASD.Experimental neurology · 2024Article
- Sleep disturbance in Angelman syndrome patients.Orphanet journal of rare diseases · 2024Review
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- UBE3A deficiency-induced autophagy is associated with activation of AMPK-ULK1 and p53 pathways.Experimental neurology · 2023Article
- The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.Stem cell reports · 2023Article
- Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists.International journal of molecular sciences · 2023Article
- The Hippocampal Response to Acute Corticosterone Elevation Is Altered in a Mouse Model for Angelman Syndrome.International journal of molecular sciences · 2022Article
- Gene dosage changes in KCTD13 result in penile and testicular anomalies via diminished androgen receptor function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors.Oncogene · 2022Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we found that the E6-associated protein (E6-AP/UBE3A) directly interacts with and coactivates the transcriptional activity of the human progesterone receptor (PR) in a hormone-dependent manner. E6-AP also coactivates the hormone-dependent transcriptional activities of the other members of the nuclear hormone receptor superfamily. Previously, it was shown that E6-AP serves the role of a ubiquitin-protein ligase (E3) in the presence of the E6 protein from human papillomavirus types 16 and 18. Our data show that the ubiquitin-protein ligase function of E6-AP is dispensable for its ability to coactivate nuclear hormone receptors, showing that E6-AP possesses two separable independent functions, as both a coactivator and a ubiquitin-protein ligase. Disruption of the maternal copy of E6-AP is correlated with Angelman syndrome (AS), a genetic neurological disorder characterized by severe mental retardation, seizures, speech impairment, and other symptoms. However, the exact mechanism by which the defective E6-AP gene causes AS remains unknown. To correlate the E6-AP coactivator function and ubiquitin-protein ligase functions with the AS phenotype, we expressed mutant forms of E6-AP isolated from AS patients and assessed the ability of each of these mutant proteins to coactivate PR or provide ubiquitin-protein ligase activity. This analysis revealed that in the majority of the AS patients examined, the ubiquitin-protein ligase function of E6-AP was defective whereas the coactivator function was intact. This finding suggests that the AS phenotype results from a defect in the ubiquitin-proteosome protein degradation pathway.
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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.