KOPS - The Institutional Repository of the University of Konstanz

Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants

Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants

Cite This

Files in this item

Files Size Format View

There are no files associated with this item.

OFFENSPERGER, Fabian, Franziska MÜLLER, Jasmin JANSEN, Daniel HAMMLER, Kathrin H. GÖTZ, Andreas MARX, Carissa L. SIROIS, Stormy J. CHAMBERLAIN, Florian STENGEL, Martin SCHEFFNER, 2020. Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants. In: Cell chemical biology. ISSN 2451-9456. eISSN 2451-9448. Available under: doi: 10.1016/j.chembiol.2020.08.017

@article{Offensperger2020-09-14Ident-51153, title={Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants}, year={2020}, doi={10.1016/j.chembiol.2020.08.017}, issn={2451-9456}, journal={Cell chemical biology}, author={Offensperger, Fabian and Müller, Franziska and Jansen, Jasmin and Hammler, Daniel and Götz, Kathrin H. and Marx, Andreas and Sirois, Carissa L. and Chamberlain, Stormy J. and Stengel, Florian and Scheffner, Martin} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/51153"> <dc:creator>Müller, Franziska</dc:creator> <dc:creator>Marx, Andreas</dc:creator> <dc:creator>Sirois, Carissa L.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:contributor>Stengel, Florian</dc:contributor> <dc:contributor>Offensperger, Fabian</dc:contributor> <dc:contributor>Hammler, Daniel</dc:contributor> <dc:creator>Offensperger, Fabian</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/51153"/> <dc:creator>Hammler, Daniel</dc:creator> <dc:creator>Stengel, Florian</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-10-01T09:51:11Z</dcterms:available> <dc:contributor>Chamberlain, Stormy J.</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dc:contributor>Götz, Kathrin H.</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Müller, Franziska</dc:contributor> <dc:contributor>Jansen, Jasmin</dc:contributor> <dcterms:title>Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants</dcterms:title> <dc:contributor>Marx, Andreas</dc:contributor> <dc:contributor>Sirois, Carissa L.</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:creator>Chamberlain, Stormy J.</dc:creator> <dc:creator>Scheffner, Martin</dc:creator> <dcterms:abstract xml:lang="eng">Genetic aberrations of the UBE3A gene encoding the E3 ubiquitin ligase E6AP underlie the development of Angelman syndrome (AS). Approximately 10% of AS individuals harbor UBE3A genes with point mutations, frequently resulting in the expression of full-length E6AP variants with defective E3 activity. Since E6AP exists in two states, an inactive and an active one, we hypothesized that distinct small molecules can stabilize the active state and that such molecules may rescue the E3 activity of AS-derived E6AP variants. Therefore, we established an assay that allows identifying modulators of E6AP in a high-throughput format. We identified several compounds that not only stimulate wild-type E6AP but also rescue the E3 activity of certain E6AP variants. Moreover, by chemical cross-linking coupled to mass spectrometry we provide evidence that the compounds stabilize an active conformation of E6AP. Thus, these compounds represent potential lead structures for the design of drugs for AS treatment.</dcterms:abstract> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-10-01T09:51:11Z</dc:date> <dc:language>eng</dc:language> <dc:contributor>Scheffner, Martin</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Götz, Kathrin H.</dc:creator> <dcterms:issued>2020-09-14</dcterms:issued> <dc:creator>Jansen, Jasmin</dc:creator> </rdf:Description> </rdf:RDF>

This item appears in the following Collection(s)

Search KOPS


Browse

My Account