Analysis of DIAP2 Rescue of diap1 Mutant Cells in Drosophila

Faculty Mentor: Pascal Meier Programmed cell death, known as “apoptosis,” is an essential part of development and the maintenance of healthy tissues in organisms. Mutated or harmful cells also self-destruct via apoptosis, thereby pre- venting their own proliferation and the development of tumors. In fact, many tumors are characterized not only by the over proliferation of damaged cells but also by the lack of sufficient apoptosis. Interference with the activation and/or success of the cell death machinery can occur at many different steps in the apoptotic pathway. In this study, Drosophila melanogaster was used to analyze the role of Inhibitor of Apoptosis Proteins (IAPs) in the cell death pathway. IAPs are believed to be one of the last steps in the prevention of cell death by the organism. These proteins bind caspases, which are responsible for cleaving the proteins within a cell and causing apopto- sis. Caspases may only be activated when not bound by an IAP. Drosophila have two known IAPs, DIAP1 and DIAP2. Without a func- tional DIAP1, cells are generated but soon after, die by apoptosis. Conversely, cells not expressing DIAP2 are viable and healthy but are sen- sitized to stress-induced cell death. In this study, mitotic recombination clones of diap1 homozygous mutant cells overexpressing DIAP2 were generated in the Drosophila eye to test whether DIAP2 overexpression can rescue the diap1 mutant lethal genotype. Rescue was tested in both the adult eye and larval imaginal disc. While significant rescue was observed in the adult eye, no rescued cell clones were present in the larval imaginal disc. This suggests that DIAP2 overexpression may play a role in cell death rescue by allowing diap1 mutant cells to survive longer during early development. In this way, the rescued cells have more time to send out proliferative signals to neighboring wild type cells, encouraging the wild type cells to divide and compensate for the death of the mutant cells. From the Washington University Undergraduate Research Digest: WUURD, Volume 2, Issue 2, Spring 2007. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Co-editor