Temporal proteasome disruption has a long term and irreversible negative impact on drosophila
Item
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Title
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Temporal proteasome disruption has a long term and irreversible negative impact on drosophila
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Identifier
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d_2009_2013:81e30d845975:10956
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identifier
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11146
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Creator
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Yeh, Chun-Hung,
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Contributor
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Thomas Schmidt-Glenewinkel
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Date
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2011
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Language
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English
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Publisher
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City University of New York.
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Subject
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Molecular biology | Genetics | Drosophila | Proteasome
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Abstract
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The presence of unfolded, misfolded, mutant and/or oxidized proteins is a severe and never ending threat to cell survival. To prevent these abnormal proteins to form aggregates and disrupt cellular homeostasis, these proteins can be delivered to the ubiquitin proteasome system (UPS) for degradation. To investigate the proteotoxic effects induced by a dysfunctional UPS, we developed a Drosophila model with "tunable" proteasome impairment by modulating the expression of one of its catalytic subunits, the dâ5 subunit, through double-stranded RNA interference (RNAi). Expression of the dbeta5 RNAi is controlled by an RU486 inducible Act5C promoter. Reduction of dbeta5 subunit expression is caused by RU486 administration. The loss of dbeta5 function causes an early onset of reduced proteasome activity. Disruption of proteasome activity has negative impacts including ubiquitinated-protein accumulation, a shorter lifespan, low resistance to oxidative stress, and locomotor dysfunction. Many UPS-impaired models are established to address effects caused by proteasome dysfunction. However, no model investigates whether temporal proteasome disruption causes long term or irreversible effects. To address this issue, temporal proteasome disruption was induced by varying the period of RU486 administration via the conditional Gene-Switch binary system. Our results demonstrate that temporal proteasome disruption causes long term/irreversible and negative effects on lifespan, protein degradation, elimination of aggregates, and locomotor activity. Taken together, these results indicate that UPS plays critical roles in maintenance of cellular function. Proteasome disruption, even just temporally, has a long term and negative impact in drosophila.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biochemistry
