Date of Award
2007
Degree Type
Thesis
Degree Name
Master of Science
Program
Pharmacology and Toxicology
Supervisor
Dr. Sean Cregan
Abstract
DNA damage, oxidative stress, and ER stress are involved in the pathogenesis of acute and chronic neurodegenerative conditions. However, the signalling pathways that activate neuronal apoptosis in response to these stressors are not well understood. Here, we demonstrate that the Bcl-2 Homology Domain 3-only (BH3- only) family member Puma is transcriptionally upregulated in response to DNA damage, oxidative stress, and ER stress. Moreover, PUMA is essential for neuronal apoptosis in these contexts. Cyclin-dependent kinase 4/6 (cdk 4/6) activation has been implicated in triggering neuronal cell death processes. In this study, we have shown that the cdk 4/6 inhibitors flavopiridol, pl6INK4a, and dominant negative-cdk 4 (DN-cdk 4) block stress-induced Puma transcription and apoptotic processes in neurons. Taken together, these results indicate that transcriptional induction of the Puma gene through cyclin-dependent kinases is critical for initiating apoptosis in response to neurodegenerative-associated stresses.
Recommended Citation
Fuerth, Ben, "CYCLIN-DEPENDENT KINASE 4/6 ENABLES PUMA INDUCTION DURING NEURONAL APOPTOSIS" (2007). Digitized Theses. 4989.
https://ir.lib.uwo.ca/digitizedtheses/4989