| Budget Amount *help |
¥119,080,000 (Direct Cost: ¥91,600,000、Indirect Cost: ¥27,480,000)
Fiscal Year 2006: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2005: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000)
Fiscal Year 2004: ¥36,270,000 (Direct Cost: ¥27,900,000、Indirect Cost: ¥8,370,000)
Fiscal Year 2003: ¥34,450,000 (Direct Cost: ¥26,500,000、Indirect Cost: ¥7,950,000)
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| Research Abstract |
Programmed cell death and neurodegeneration occur in the brain. To elucidate the mechanisms of neural cell death including neurodegeneration, we developed a novel screen for genes involved in the neuronal cell death associated with neurodegeneration, involving the overexpression of individual genes throughout much of the Drosophila genome (GS screening). As a result of the screen of approximately 5000 fly strains, we identified and characterized the endd2 gene, which encodes the Drosophila ortholog of Sec61α (DSec61α) located in endoplasmic reticulum, as a new component of the neural cell death and degeneration pathways. We then performed a dominant-modifier screen of reaper for identification of neural-cell death related genes using a set of deficiency strains that cover more than 70% of the Drosophila genome. In this screening, we identified DmIKKε as a candidate component in the pathway of Reaper-induced cell death. DmIKKε was also identified as a candidate gene of neural cell death promoting gene in GS screening. Biochemical studies indicated that DmIKKε that promotes degradation of Drosophila IAP (DIAP 1) through direct phosphorylation. Inactivation of DmIKKε causes DIAP 1 accumulation without affecting developmental cell death. DmIKKε is a DIAP 1-degrading kinase that regulates endogenous levels of DIAP 1, which in turn regulates neural cell fate through non-apoptotic functions of caspases in vivo.
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