NAVRACHANA UNIVERSITY

Functional characterization of dosage-dependent lethal mutation of ubiquitin in saccharomyces cerevisiae

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dc.contributor.author Doshi, Ankita
dc.contributor.author Mishara, Pradeep
dc.contributor.author Sharma, Mrinal
dc.contributor.author Prabha, C. Ratna
dc.date.accessioned 2021-12-16T06:38:34Z
dc.date.available 2021-12-16T06:38:34Z
dc.date.issued 2014-11
dc.identifier.issn 1567-1356
dc.identifier.uri http://27.109.7.66:8080/xmlui/handle/123456789/763
dc.description FEMS yeast research, 2014 Nov;14(7) en_US
dc.description.abstract Ubiquitin is a eukaryotic protein with 96% sequence conservation from yeast to human. Ubiquitin plays a central role in protein homeostasis and regulation of protein function. We have reported on the generation of variants of ubiquitin by in vitro evolution in Saccharomyces cerevisiae to advance our understanding of the role of the invariant amino acid residues of ubiquitin in relation to its function. One of the mutants generated, namely UbEP42, was a dosage-dependent lethal form of the ubiquitin gene, causing lethality to UBI4-deficient cells but not to ubiquitin wild-type cells. In the present study we investigated the functional reasons for the observed lethality. Expression of UbEP42 in a UBI4-deleted stress-sensitive strain resulted in an increased generation time due to a delayed S phase caused by decreased levels of Cdc28 protein kinase. Cells expressing UbEP42 displayed heightened sensitivity towards heat stress and exposure to cycloheximide. Furthermore, its expression had a negative effect on the degradation of substrates of the ubiquitin fusion degradation pathway. However, UbEP42 is incorporated into polyubiquitin chains. Collectively, our results establish that the effects seen with the mutant ubiquitin protein UbEP42 are not due to malfunction at the stage of polyubiquitination. en_US
dc.language.iso en en_US
dc.publisher FEMS yeast research en_US
dc.subject functions of ubiquitin en_US
dc.subject in vitro evolution of ubiquitin en_US
dc.subject mutations in ubiquitin en_US
dc.subject structure of ubiquitin en_US
dc.subject ubiquitin en_US
dc.title Functional characterization of dosage-dependent lethal mutation of ubiquitin in saccharomyces cerevisiae en_US
dc.type Article en_US


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