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

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Title: The Effect of Noxa Serine-13 Phosphorylation on Hyperthermia-Induced Apoptosis
Author: Morey, Trevor
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Mosser, Richard
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.
Date: 2012-01
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