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dc.contributor.authorO. Ilyinskii, Petr
dc.contributor.authorV. Nurminskaya, Maria
dc.contributor.authorL. Gabai, Vladimir
dc.contributor.authorG. Prilipov, Alexei
dc.contributor.authorV. Usachev, Evgeny
dc.contributor.authorG. Zakharova, Lyudmila
dc.contributor.authorThoidis, Galini
dc.contributor.authorD. Altstein, Anatoly
dc.contributor.authorM. Shneider, Alexander
dc.date.accessioned2017-05-03T15:30:48Z
dc.date.available2017-05-03T15:30:48Z
dc.date.issued2009
dc.date.modified2010-10-15T07:27:53Z
dc.identifier.issn15578100
dc.identifier.doi10.1089/omi.2009.0006
dc.identifier.urihttp://hdl.handle.net/10072/34365
dc.description.abstractInadvertent cytotoxicity may hinder the expression of many recombinant proteins that are of industrial or medicinal importance. Here, we show that covalent binding of the influenza A cytotoxic protein M2 to a polyglutamine domain (polyQ-M2; QM2) results in significant delay of its cytotoxic effects when compared to wildtype protein (M2wt). We also show that while expression of recombinant M2wt from A/WSN/1933 strain could not be attained in vaccinia virus (VV), polyQ-M2 was successfully expressed in this system. Moreover, we demonstrate that in cell culture, the polyQ domain is cleaved off following 48 h of expression, thus releasing free and active M2. Similarly, we show the spontaneous cleavage and polyQ release from fusion with another distinct polypeptide, green fluorescent protein (GFP). Expression of M2 from QM2 construct was more prolonged than one based on M2wt-expressing construct, markedly exceeding it at the later time points. Therefore, cell death caused by a toxic polypeptide may be suppressed via genetic fusion with polyQ, resulting in its enhanced expression, followed by slow release of the free polypeptide from the fusion. Collectively, covalent fusion with polyQ or other aggregate-forming domains presents a novel approach for industrial production of cytotoxic proteins and also holds promise for gene therapy applications.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMary Ann Liebert, Inc.
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom211
dc.relation.ispartofpageto217
dc.relation.ispartofissue3
dc.relation.ispartofjournalOMICS: A Journal of Integrative Biology
dc.relation.ispartofvolume13
dc.rights.retentionY
dc.subject.fieldofresearchProteins and Peptides
dc.subject.fieldofresearchGene Expression (incl. Microarray and other genome-wide approaches)
dc.subject.fieldofresearchVirology
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchcode030406
dc.subject.fieldofresearchcode060405
dc.subject.fieldofresearchcode060506
dc.subject.fieldofresearchcode06
dc.titleEffective Expression of Recombinant Cytotoxic Protein via Its Attachment to a Polyglutamine Domain
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2009 Mary Ann Liebert, Inc., publishers. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
gro.date.issued2009
gro.hasfulltextNo Full Text
gro.griffith.authorUsachev, Evgeny


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