Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity of various substrates is associated with cell morphological changes. Despite their importance in apoptosis, caspase regulatory mechanisms and substrates remain largely unknown. Some recent reports have revealed non-apoptotic functions for caspases, including autophagy. Therefore, I searched for modifiers of DCP-1 by screening enhancer and promoter element inserted Drosophila melanogaster lines (EP lines) for dominant suppressors of the Dcp-1 phenotype.
I screened 15,000 EP lines for dominant modifiers of the GAL4-induced UAS-Dcp-1 eye phenotype and identified 72 Dcp-1 -interacting genes that were classified into ve groups based on their functions and pathways. Suppressors of the Dcp-1 overexpression phenotype consisted of nine autophagy-related genes. Generally, MAP kinase genes enhanced the Dcp-1 effect of this phenotype, and as predicted, many transcription factors also enhanced or were enhanced by DCP-1. Additionally, I identified several novel genes that interacted with Dcp-1. Expression of Atg8b-GFP, an indicator of autophagy, was detected in Dcp-1 eye imaginal discs and in the S2 cell line with full-length DCP-1 induction. Co-expression of DCP-1 and eGFP-Atg5 rescued the eye phenotype in adults and reduced cell death in larval eye imaginal discs. I analyzed the differences between full-length autophagy-inducing and truncated apoptosis-inducing DCP-1 using S2 cell cultures. I found the interrelation between caspase and autophagy-related genes by caspase activity test and expression level test. Also I found that the DCP-1 roles in Drosophila oogenesis. DCP-1 is necessary to induce autophagic cell death in oogenesis in starvation. After all, this phenomenon regulates fecundity against the starvation finally.
I identified several interesting Dcp-1 modifiers that reduced DCP-1-induced cell death. More importan...