Year: 2014
Type: dissertation
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.
Author: Rebecca L. Rumney
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2542864145