Identification of autophagic characteristics and functions of drosophila caspase DCP-1 = 초파리 caspase DCP-1 의 autophagy 에서의 특성과 역할에 대한 규명

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Background 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. Results 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. Conclusions I identified several interesting Dcp-1 modifiers that reduced DCP-1-induced cell death. More importan...
Yoo, Ook-Joonresearcher유욱준researcher
한국과학기술원 : 생명과학과,
Issue Date
327725/325007  / 020045048

학위논문(박사) - 한국과학기술원 : 생명과학과, 2009. 8., [ vii, 75, 8 p. ]


Drosophila; autophagy; caspase; cell death; screening; 초파리; 오토파지; 캐스페이즈; 세포사멸; 스크리닝; Drosophila; autophagy; caspase; cell death; screening; 초파리; 오토파지; 캐스페이즈; 세포사멸; 스크리닝

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