Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Outline of Final Research Achievements |
SREBP-1 is the master regulator of lipid synthesis, and recently we identified a novel protease (proteaseX) that activates SREBP-1. In this study, we aimed to clarify the mechanisms of SREBP-1 activation and lipid metabolism by proteaseX. We analyzed the mechanisms of SREBP-1 activation by overexpression or knockout of proteaseX in vitro and in vivo. We found that proteaseX activates SREBP-1 and its target lipogenic genes expressions by cleavage of SREBP-1. ProteaseX and SREBP-1 were co-localized in the ER, and proteaseX interacted with SREBP-1-SCAP-Insig complex. In mouse experiments, activated SREBP-1 and lipid synthesis genes expressions were decreased in proteaseX knockout mice on western diet (WD) compared with wild-type mice on WD. These results suggest that proteaseX is required for activating SREBP-1 and lipid metabolism in response to nutrient overload.
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