Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/112508
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dc.contributor.authorWortham, N.en
dc.contributor.authorProud, C.en
dc.date.issued2015en
dc.identifier.citationBMC Medical Genetics, 2015; 16(1):64-1-64-8en
dc.identifier.issn1471-2350en
dc.identifier.issn1471-2350en
dc.identifier.urihttp://hdl.handle.net/2440/112508-
dc.description.abstractBACKGROUND: Leukoencephalopathy with Vanishing White Matter (VWM) is an autosomal recessive disorder caused by germline mutations in the genes EIF2B1-5, which encode the 5 subunits of the eukaryotic translation initiation factor eIF2B. To date, analysis of the biochemical effects of mutations in the EIF2B2-5 genes has been carried out, but no study has been performed on mutations in the EIF2B1 gene. This gene encodes eIF2Bα, the smallest subunit in eIF2B which has an important role in both the structure and regulation of the eIF2B complex. METHODS: eIF2B subunits were overexpressed in HEK293 cells and isolated from the resulting cell lysates by affinity chromatography. Formation of the eIF2B complex and binding of its substrate, eIF2, was assessed by western blot. Assays of the guanine nucleotide exchange (GEF) activity were also carried out. RESULTS: Of the 5 eIF2Bα mutations studied, we found 3 that showed loss or reduction of binding of eIF2Bα to the rest of the complex, one with increased GEF activity, and one where no effects on activity or complex formation were observed. CONCLUSIONS: This is the first study on eIF2Bα VWM mutations. We show that some mutations cause expected decreases in GEF activity or complex formation, similar to a majority of observed VWM mutations. However, we also observe some unexpected changes which hint at other effects of these mutations on as yet undescribed functions of eIF2B.en
dc.description.statementofresponsibilityNoel C. Wortham, and Christopher G. Prouden
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rights© 2015 Wortham and Proud. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectHumans; Eukaryotic Initiation Factor-2B; Protein Subunits; Blotting, Western; Chromatography, Affinity; Mutagenesis, Site-Directed; Protein Binding; Mutation; Plasmids; Models, Molecular; Leukoencephalopathies; HEK293 Cellsen
dc.titleBiochemical effects of mutations in the gene encoding the alpha subunit of eukaryotic initiation factor (eIF) 2B associated with Vanishing White Matter diseaseen
dc.typeJournal articleen
dc.identifier.rmid0030035750en
dc.identifier.doi10.1186/s12881-015-0204-zen
dc.identifier.pubid213073-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.library.teamDS01en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidProud, C. [0000-0003-0704-6442]en
Appears in Collections:Molecular and Biomedical Science publications

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