| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
ATG-ubiquitylation-like modification is essential for autophagy in yeast, plant, and mammals. ATG7 is a key enzyme essential for the reaction. We generated a conditional knock-out mouse of ATG7 Mouse liver lacking Atg7 resulted in a severe hepatomegaly with inflammation, leading to a loss of viability under starvation. During generating the conditional mouse, we showed that human Atg4B is an unique cysteine protease for carboxyl cleavage of LC, GABARAP, and GATE-16, and is delipidating enzyme for LC3-and GABARAP-phospholipid conjugate. Furthermore, we showed that human LC3 is an authentic modifier mediated by human Atg7 and Atg3. We also found a novel Ufml Ubl-modification system in mammals. In addition, we investigated several aspects of ATG-conjugation systems; Strauctural analysis of LC3 by NMR, Role of Rab7 in autophagy, and tissue-distribution of modified forms of LC3, GABARAP, and GATE-16. Now, we are generating a brain-specific ATG7-knockout mouse that will be a definitive tool for analyses of relations between autophagy and neurodegenerative diseases
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