Mdm2-p53 Signaling in Tissue Homeostasis and the DNA Damage Response: A Dissertation

The dissertation explored the critical role of the Mdm2-p53 signaling pathway in tissue homeostasis and the DNA damage response, using genetically engineered mouse models. It demonstrated that Mdm2 is essential for regulating p53 activity to maintain normal stem cell function, as its deletion in epidermal progenitor cells led to hair loss and skin aging due to increased p53 activity. Additionally, the study investigated the impact of Mdm2 phosphorylation on p53 stability, revealing that the absence of a specific phosphorylation site reduced p53 stability and increased tumorigenesis, while a phosphomimic model showed prolonged p53 activation. These findings highlighted the importance of Mdm2 in controlling p53 activity and its implications for tumor suppression and cellular stress responses.