| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Outline of Final Research Achievements |
A membrane-anchoring protein p18, which is localizing onto late endosomes and lysosomes, takes roles to regulate cell growth and intracellular membrane trafficking. Here, the kinase signal pathways interacting with p18 were analyzed and we found that mTORC1 and its downstream effects including the change of gene expression is the major path of membrane trafficking regulation. As to the cell growth control, we found that mTORC2 is activated by the suppression of mTORC1 in p18 knockout cells, and activated mTORC2 induces the expression of cell cycle inhibitor proteins through the SGK1-FoxO3a axis. To access the physiological importance of p18 in vivo, a keratinocyte-specific conditional p18 knockout mouse was generated, and we found that p18 act as an essential regulator for keratinocyte differentiation and epidermal barrier formation. These results indicate that p18 and associated kinase signals are crucial for tissue formation and the regulation of cellular function.
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