Induction of apoptosis or cell cycle arrest by two human wildtype variants of the p53 protein

• Main Author: Azoulay, Eric.
• Other Authors: Matlashewski, Greg (advisor)
• Format: Others
• Language: en
• Published: McGill University 1999
• Subjects: p53 antioncogene.; DNA-binding proteins.; Apoptosis.; Cell cycle.
• Online Access: http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30337

The human wildtype p53 tumor suppressor gene is found in two different forms, p53 Arginine and p53 Proline. This difference results in a substitution of a proline for an arginine at codon 72 producing the polymorphism. Knowing that apoptosis and cell cycle arrest are the two main functions of p53, the objective of this project was to determine the difference in the capacity of these allelic variants of p53 to induce apoptosis and/or cell cycle arrest in two different experimental model systems. The first experimental system was composed of non-transformed 10(1) cells and the second one was transformed Saos-2 cells. In the first experimental system, the two wildtype forms of p53 induced cell cycle arrest at the same level and did not induce apoptosis. On the other hand, in transformed cells, both p53Arg and p53Pro induced apoptosis at similar levels. No cell cycle arrest activity has been detected in Saos-2 cells. In conclusion, this study suggests that the induction of cell cycle arrest or apoptosis depends more on the cell type than on the type of the p53 protein. Also, the intensity of cell cycle arrest or apoptosis is independent of which allelic variant of p53 is present under the experimental conditions used in this study.