N-terminal hydrophobic amino acids of ATF5 confer IL-1{beta}-induced stabilization [Immunology]

December 30th, 2013 by Abe, T., Kojima, M., Akanuma, S., Iwashita, H., Yamazaki, T., Okuyama, R., Ichikawa, K., Umemura, M., Nakano, H., Takahashi, S., Takahashi, Y.

Activating transcription factor 5 (ATF5) is a stress-response transcription factor that responds to amino acid limitation and exposure to cadmium chloride (CdCl2) and sodium arsenite (NaAsO2). The N-terminal amino acids contribute to destabilization of the ATF5 protein in steady-state conditions and serve as a stabilization domain in stress-response after CdCl2 or NaAsO2 exposure. In this study, we showed that interleukin 1β (IL-1β), a proinflammatory cytokine, increased the expression of ATF5 protein in HepG2 hepatoma 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-1β-response domain. Furthermore, IL-1β increased the translational efficiency of ATF5 mRNA via the 5′-untranslated region α (5′-UTRα) and phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). ATF5 knockdown in HepG2 cells upregulated the IL-1β-induced expression of serum amyloid A 1 (SAA1) and SAA2 genes. Our results showed that the N-terminal hydrophobic amino acids play an important role in the regulation of ATF5 protein expression in IL-1β-mediated immune response and that ATF5 is a negative regulator for IL-1β-induced expression of SAA1 and SAA2 in Hep G2 cells.