Tumor suppressor p53 is a mediator of stress-induced cell cycle arrest and apoptosis. The kinase inhibitor 2-aminopurine (2-AP) is an adenine analog shown to cause cells to bypass DNA damage-induced cellular arrest through unknown mechanisms, and may potentially target p53. Although p53 plays vital roles in adaptation to many stresses, its role in cellular response to endoplasmic reticulum (ER) stress is unclear. Here, stress-induced p53 stabilization and checkpoint control in the presence of 2-AP are examined, as well as p53 regulation upon ER stress induction. I show that 2-aminopurine suppresses p53 stabilization in response to different forms of DNA damage. Biologically, 2-AP exposure enables cells to bypass adriamycin-induced G2/M arrest in a p53-dependent manner, but rescues the clonogenic survival of cells exposed to adriamycin in a p53-independent manner. Next, I show that pharmacological and physiological inducers of ER stress can inhibit stress-induced p53 function by promoting p53 cytoplasmic retention.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.78384 |
| Date | January 2003 |
| Creators | Huang, Shirley Chien-Chieh, 1978- |
| Contributors | Koromilas, Antonis E. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001976407, proquestno: AAIMQ88219, Theses scanned by UMI/ProQuest. |
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