The role of HSF1 in the heat induced expression of the Bcl-2 family member Noxa

Abstract

The Bcl-2 family of proteins play essential roles in regulating the process of stress-induced apoptosis. The BH3-only members of this family act as stress sensors that can be activated by transcriptional and post-translational mechanisms by a variety of cellular insults. Identifying the exact mechanisms by which the BH3-only proteins are regulated is critical to the understanding of the apoptotic pathway and assist in identifying potential therapeutic targets for various diseases. This thesis demonstrates that the BH3-only protein Noxa is induced following hyperthermia via an increase in transcriptional activity of the 'Noxa' gene. Additionally, modulating the activity of HSF1 via activators and inhibitors have direct affects on both Noxa protein and mRNA levels. 'Noxa' promoter analysis proved to be inconclusive in identifying a potential HSE that could be responsible for the increase in 'Noxa' transcription following hyperthermia. However, a potential role for HSF1 in Noxa regulation following heat shock appears likely.