A thesis submitted in partial fulfillment of the requirements for the Masters of Arts in the Department of Biology.
The tumor suppressor gene, p53, is an important cell cycle regulatory protein. Activation of p53 can cause the cell cycle to arrest or lead to apoptosis. If cells did not undergo cycle arrest or apoptosis then they would grow out of control and become cancerous (16, 31, 39). The purpose of this research was to understand the role of p53 in stress-induced apoptotic pathways. The two forms of stress administered to p53 +/+, +/- and -/- (strain B6.129S2-Trp53tm1Tyj) mice were ionizing radiation and cisplatin. Following exposure to radiation or cisplatin, the mice were sacrificed at various time points and their testes were removed. Western analyses were performed on the left testis homogenates to compare relative p53 levels over time. The right testis was made into sections on slides, and was then stained for apoptotic germ cells using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Comparison of p53 expression levels to levels of apoptotis over time provided a time frame of p53’s role in apoptotic pathways.
In both the radiation and cisplatin groups, p53 appeared to play a role in apoptosis. Following exposure to radiation and cisplatin, p53 levels increased. Similar to the effects observed with p53, apoptosis levels increased indicating a link between p53 and apoptosis. Apoptosis was shown to occur in mice that did not have p53, just at lower levels compared to mice that did have p53. This indicates that although p53 plays an important role in apoptotic pathways, there are p53-independent apoptotic pathways. A testable model explaining p53’s role in apoptotic pathways as well as p53-independent apoptotic pathways is proposed.
Digital Initiatives Press: Rhode Island College
p53, protein, Apoptotic, cycle arrest
Genetic Processes | Genetic Structures
Lamkin, Jamie, "Investigating the Role of p53 in the Germ Cell Apoptotic Pathway" (2011). Ebook Gallery. 10.