Identification and Characterization of Novel Nematode Cell Death Genes and Their Mammalian Homologs

摘要

Apoptosis is a major determinant in the ability of cells to become cancerous. The aim of this grant was to identify conserved regulators of apoptosis using the nematode C. elegans as a model system. Specifically, we searched for proteins that interact with CED-9, the nematode homolog of the oncoprotein Bcl-2. We found that CED-9 interacts with CED-4, the worm homolog of the apoptotic regulator Apaf- 1, and characterised the regulation of CED-9 by EGL-1, a BH3 domain protein that also directly binds to CED-9. Finally, we identified a dozen additional C. elegans proteins that interacted with both CED- 9 and Bcl-2 in a yeast two-hybrid system. Unfortunately, none of these proteins showed any significant effect on nematode apoptosis, either when overexpressed or inactivated by RNA interference.