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Regulation of heat-induced cell death by the pro-apoptotic Bcl-2 family protein PUMA

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dc.contributor.advisor Mosser, Richard D. Rumney, Rebecca Lee-Anne 2014-09-09T18:33:03Z 2015-08-28T05:00:27Z 2014-08 2014-08-28 2014-09-09
dc.description.abstract Apoptosis is often deregulated in a number of human diseases. Hyperthermia induced apoptosis is a model system for studying the consequences of protein misfolding and is mediated by the Bcl-2 family of proteins. This family consists of both pro-apoptotic and anti-apoptotic members that control mitochondrial integrity. The BH3-only pro-apoptotic members are strong inducers of apoptosis. Our examination of the effect of hyperthermia on the BH3-only protein PUMA, found that although protein levels were rapidly depleted following exposure to heat shock, levels of PUMA mRNA increased. This suggests that post-transcriptional mechanisms control the translation of PUMA mRNA in heat-shocked cells. We therefore examined whether miRNA-mediated inhibition of PUMA translation was responsible for the loss of PUMA protein. We provide evidence for the role of miR-24-2 and miR-29a as mediators of this repression and that strategies directed at the inhibition of these miRNAs could be effective in sensitizing cells to heat-induced apoptosis. en_US
dc.description.sponsorship NSERC en_US
dc.language.iso en en_US
dc.rights Attribution-NoDerivs 2.5 Canada *
dc.rights.uri *
dc.subject Apoptosis en_US
dc.subject PUMA en_US
dc.subject HSP70 en_US
dc.subject miRNA en_US
dc.title Regulation of heat-induced cell death by the pro-apoptotic Bcl-2 family protein PUMA en_US
dc.type Thesis en_US Molecular and Cellular Biology en_US Master of Science en_US Department of Molecular and Cellular Biology en_US
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Attribution-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NoDerivs 2.5 Canada