N-terminal hydrophobic amino acids of ATF5 protein confer IL-1b-induced stabilization, and responsible for the suppression of the serum amyloid A1 (SAA1) ans SAA2 gene expression

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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.