Year: 2015
Type: dissertation
Abstract: Mutation or loss of TP53 has been detected in more than 50% of all human tumours. Gain-of-function (GOF) TP53 mutations have been linked to metastasis, altered metabolism, and drug resistance. Cancer patients carrying GOF TP53 mutations in their tumours respond poorly to standard of care treatments and have a worse prognosis. In my Master's thesis, I have focused on understanding the relationship between a frequently observed mutation of TP53 (TP53R248W), and BTRC, an E3 ubiquitin ligase with functions impinging on cell cycle, morphology and metabolism. I observed a correlation between BTRC protein expression and TP53 genotype across a panel cancer cell lines. Additionally, I observed that TP53R248W-mediated regulation of BTRC expression is dependent on a post-transcriptional mechanism, likely involving more than one micro-RNA. In conclusion, I present a model describing the regulation of BTRC by TP53, which may have implications for targeted strategies in cancers harboring GOF TP53 mutations.
Source: TSpace (University of Toronto)
Author: Wei Xu
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2564895100