| Project/Area Number |
22590293
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Metropolitan Institute of Medical Science (2011-2012)
Juntendo University (2010) |
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Principal Investigator |
ICHIMURA Yoshinobu 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (80400993)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMATSU Masaaki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (90356254)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 選択的オートファジー / p62 / LC3 / オートファジー |
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| Research Abstract |
p62 is a scaffold protein involved in multiple signaling pathways, and its intracellular levels are constitutively and selectively regulated by basal autophagy. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy receptors/specific substrates. LC3, a mammalian Atg8 homolog, interacts directly with p62 by LIR (LC3 interacting region), highly conserved sequence among p62 homologs, and thus p62 is trapped into autophagosome. In contrast to the single Atg8p in yeast, mammals have 6 homologues of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. In this study, we found that simultaneous knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, and knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62. These results suggest that while mammalian Atg8 homologues are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologues.
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