| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
In this study, we show that IL-1b, a proinflammatory cytokine, increases the expression of ATF5 protein in HepG2 cells in part by stabilizing the ATF5 protein. The N-terminal domain rich in hydrophobic amino acids that is predicted to form a hydrophobic network was responsible for destabilization in steady-state conditions and served as an IL-1b response domain. Furthermore, IL-1b increased the translational efficiency of ATF5 mRNA via the 5' UTR a and phosphorylation of the eukaryotic translation initiation factor 2a (eIF2a). ATF5 knockdown in HepG2 cells up-regulated the IL-1b-induced expression of the serum amyloid A1 (SAA1) and SAA2 genes. Our results show that the N-terminal hydrophobic amino acids play an important role in the regulation of ATF5 protein expression in IL-1b-mediated immune response and that ATF5 is a negative regulator for IL-1b-induced expression of SAA1 and SAA2 in HepG2 cells.
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