Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Dr. Shawn Li

Abstract

Apoptosis is an essential process in development and tissue maintenance. The tumor suppressor protein p53 initiates apoptosis through transactivation of pro-apoptotic genes when cellular stress is detected. This study identifies a regulatory role for the lysine demethylase, PHF8, in the p53-mediated apoptosis pathway. We initially suspected PHF8 of demethylating the adaptor protein Numb, however found this to be untrue. PHF8 has been found to have oncogenic properties including an anti-apoptotic effect, however how PHF8 negatively affects apoptosis has not been previously investigated. We found PHF8 inhibits translation of the pro-apoptotic genes TP53, BAX and CASP3. Chromatin immunoprecipitation revealed PHF8 binding to the TP53 and CASP3 gene promoters. H3K27 methylation at these promoters was significantly decreased with doxorubicin treatment in the presence of PHF8, and significantly increased when PHF8 was knocked down. Since methylated H3K27 is a repressive mark, we suspect other transcription factors or histone modifying proteins to be involved.


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