Defective immuno- and thymoproteasome assembly causes severe immunodeficiency


Dateien zu dieser Ressource

Prüfsumme: MD5:d37b09d020c78d8296caf3c10955e9de

TREISE, Irina, Eva M. HUBER, Tanja KLEIN-RODEWALD, Wolfgang HEINEMEYER, Simon A. GRASSMANN, Michael BASLER, Thure ADLER, Marcus GROETTRUP, Michael GROLL, Dirk H. BUSCH, 2018. Defective immuno- and thymoproteasome assembly causes severe immunodeficiency. In: Scientific reports. 8(1), 5975. eISSN 2045-2322. Available under: doi: 10.1038/s41598-018-24199-0

@article{Treise2018-04-13Defec-42174, title={Defective immuno- and thymoproteasome assembly causes severe immunodeficiency}, year={2018}, doi={10.1038/s41598-018-24199-0}, number={1}, volume={8}, journal={Scientific reports}, author={Treise, Irina and Huber, Eva M. and Klein-Rodewald, Tanja and Heinemeyer, Wolfgang and Grassmann, Simon A. and Basler, Michael and Adler, Thure and Groettrup, Marcus and Groll, Michael and Busch, Dirk H.}, note={Article Number: 5975} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Treise, Irina</dc:contributor> <dc:contributor>Grassmann, Simon A.</dc:contributor> <dc:contributor>Adler, Thure</dc:contributor> <dc:contributor>Klein-Rodewald, Tanja</dc:contributor> <dc:creator>Groll, Michael</dc:creator> <dc:creator>Groettrup, Marcus</dc:creator> <dcterms:issued>2018-04-13</dcterms:issued> <dc:date rdf:datatype="">2018-04-25T14:38:44Z</dc:date> <bibo:uri rdf:resource=""/> <dc:creator>Heinemeyer, Wolfgang</dc:creator> <dc:contributor>Groettrup, Marcus</dc:contributor> <dspace:isPartOfCollection rdf:resource=""/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Klein-Rodewald, Tanja</dc:creator> <dc:creator>Huber, Eva M.</dc:creator> <dcterms:hasPart rdf:resource=""/> <dc:creator>Treise, Irina</dc:creator> <dcterms:rights rdf:resource=""/> <dspace:hasBitstream rdf:resource=""/> <dcterms:available rdf:datatype="">2018-04-25T14:38:44Z</dcterms:available> <dc:contributor>Groll, Michael</dc:contributor> <dc:creator>Adler, Thure</dc:creator> <dc:creator>Busch, Dirk H.</dc:creator> <dcterms:title>Defective immuno- and thymoproteasome assembly causes severe immunodeficiency</dcterms:title> <dc:contributor>Huber, Eva M.</dc:contributor> <dcterms:abstract xml:lang="eng">By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results in the single amino acid exchange G170W in multicatalytic endopeptidase complex subunit-1 (MECL-1), the β2i-subunit of the immuno- and thymoproteasome. Yeast mutagenesis and crystallographic data suggest that the severe TUB6-phenotype compared to the MECL-1 knockout mouse is caused by structural changes in the C-terminal appendage of β2i that prevent the biogenesis of immuno- and thymoproteasomes. Proteasomes are essential for cell survival, and defective proteasome assembly causes selective death of cells expressing the mutant MECL-1, leading to the severe immunological phenotype. In contrast to the immunosubunits β1i (LMP2) and β5i (LMP7), mutations in the gene encoding MECL-1 have not yet been assigned to human disorders. The TUB6 mutant mouse line exemplifies the involvement of MECL-1 in immunopathogenesis and provides the first mouse model for primary immuno- and thymoproteasome-associated immunodeficiency that may also be relevant in humans.</dcterms:abstract> <dc:creator>Grassmann, Simon A.</dc:creator> <dcterms:isPartOf rdf:resource=""/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>Heinemeyer, Wolfgang</dc:contributor> <dc:contributor>Busch, Dirk H.</dc:contributor> <dc:creator>Basler, Michael</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Basler, Michael</dc:contributor> <dc:rights>terms-of-use</dc:rights> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 25.04.2018 (Informationen über die Zugriffsstatistik)

Treise_2-jxn08y7l42bj7.pdf 50

Das Dokument erscheint in:

KOPS Suche


Mein Benutzerkonto