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The Effect of Noxa Serine-13 Phosphorylation on Hyperthermia-Induced Apoptosis

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dc.contributor.advisor Mosser, Richard
dc.contributor.author Morey, Trevor
dc.date.accessioned 2012-02-13T14:34:50Z
dc.date.available 2013-01-26T06:00:12Z
dc.date.copyright 2012-01
dc.date.created 2012-01-26
dc.date.issued 2012-02-13
dc.identifier.uri http://hdl.handle.net/10214/3329
dc.description.abstract Regulation of apoptosis is critical for cell survival during mild stress and for proper removal of damaged cells during severe stress including hyperthermia. Previous studies have shown that knockdown of the BH3-only protein Noxa prevents hyperthermia-induced Mcl-1 degradation and activation of apoptosis. Noxa is a pro-apoptotic BH3-only protein that is able to selectively bind to and disable anti-apoptotic Mcl-1. Phosphorylation of Noxa on serine-13 by the cyclin-dependent kinase CDK5 inhibits the apoptotic function of Noxa. In this study I investigated whether hyperthermia is able to induce apoptosis by preventing Noxa phosphorylation, due to reduced CDK5 activity, leading to activation of Noxa. I was able to demonstrate that both the phosphorylation status and solubility of CDK5 is reduced during hyperthermia. Furthermore, overexpression of a non-phosphorylatable Noxa (S13A) resulted in a significant decrease in cell viability and increase in caspase-3 activity compared to overexpression of wild-type Noxa at 37°C. However, I was unable to detect in vivo phosphorylation of Noxa serine-13 in lymphoid cells and therefore was unable to conclude whether or not hyperthermia affects the phosphorylation status of Noxa. en_US
dc.language.iso en en_US
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/2.5/ca/ *
dc.subject Apoptosis en_US
dc.subject Noxa en_US
dc.subject Phosphorylation en_US
dc.subject BH3-only en_US
dc.subject CDK5 en_US
dc.subject Hyperthermia en_US
dc.title The Effect of Noxa Serine-13 Phosphorylation on Hyperthermia-Induced Apoptosis en_US
dc.type Thesis en_US
dc.degree.programme Molecular and Cellular Biology en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Molecular and Cellular Biology en_US
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