ArticleProceedings of the National Academy of Sciences of the United States of America2015
Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Members of the RhoA subfamily of GTPases suppress the stimulatory effect of the HPV E6 oncoprotein on the ubiquitin ligase E6AP.Scientific reports · 2026Article
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- Rethinking residual p53 function in HPV-positive cervical cancer cells.Journal of virology · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Autism and Human Papillomavirus (HPV) E6: A Comprehensive Review.Iranian journal of psychiatry · 2026Review
- Genome integration of human DNA oncoviruses.Journal of virology · 2025Review
- Protein semisynthesis reveals plasticity in HECT E3 ubiquitin ligase mechanisms.Nature chemistry · 2024Article
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- Electrostatic and steric effects underlie acetylation-induced changes in ubiquitin structure and function.Nature communications · 2022Article
- Insight into Viral Hijacking of CRL4 Ubiquitin Ligase through Structural Analysis of the pUL145-DDB1 Complex.Journal of virology · 2022Article
- Activation of E6AP/UBE3A-Mediated Protein Ubiquitination and Degradation Pathways by a Cyclic γ-AA Peptide.Journal of medicinal chemistry · 2022Article
- Structural and functional consequences of NEDD8 phosphorylation.Nature communications · 2021Article
- Chemical proteomic profiling reveals protein interactors of the alarmones diadenosine triphosphate and tetraphosphate.Nature communications · 2021Article
- Regulation of O-Linked N-Acetyl Glucosamine Transferase (OGT) through E6 Stimulation of the Ubiquitin Ligase Activity of E6AP.International journal of molecular sciences · 2021Article
- Loss of nuclear UBE3A activity is the predominant cause of Angelman syndrome in individuals carrying UBE3A missense mutations.Human molecular genetics · 2021Article
- Mechanistic basis for ubiquitin modulation of a protein energy landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mono-ubiquitination of Rabphilin 3A by UBE3A serves a non-degradative function.Scientific reports · 2021Article
- Adaptors as the regulators of HECT ubiquitin ligases.Cell death and differentiation · 2021Review
- A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome.Molecular genetics & genomic medicine · 2020Article
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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
Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein.
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