More than half of all cancers involve mutations of the transcription factor p53, a master regulator of cellular stress responses and apoptotic cell death. p53 is carefully controlled by many mechanisms, including ubiquitination and degradation by the ubiquitin proteasomal system (UPS). Human UBE2D2, a copper dependent E2 ubiquitin conjugating enzyme, appears to be an important regulator of p53 and cellular stress through E3 partners such as MDM2. Conversely, the mechanisms by which the UPS regulates p53 in Drosophila melanogaster have been relatively understudied. This work examines the relationships between copper, the UPS, and apoptosis in Drosophila, with the aim of better establishing the fruit fly as a model to study this regulatory network. My phenotypic and molecular analyses have established both UbcD1 (the fly orthologue of UBE2D2) and a partner protein, Companion of Reaper (Corp), as negative p53 regulators. Human UBE2D2 is also capable of regulating Drosophila p53, and copper-binding is important for this function. I have also uncovered several links between copper levels and p53-mediated apoptosis. Extreme deviations in copper levels appears to exacerbate p53-mediated apoptosis, while mild reductions in copper in the trans-Golgi network appear to have protective effects. Extreme copper deprivation through loss of the copper importer Ctr1A also generates a p53-independent apoptotic phenotype, which UbcD1 can also mediate. These findings bring us closer to understanding how the partnership between copper and this complex regulatory network allows cells to manage stress in both healthy and disease states.