N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1beta (IL-1beta)-induced stabilization.
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Abe T, Kojima M, Akanuma S, Iwashita H, Yamazaki T, Okuyama R, Ichikawa K, Umemura M, Nakano H, Takahashi S, Takahashi Y
N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1beta (IL-1beta)-induced stabilization.
J Biol Chem. 2014 Feb 14;289(7):3888-900. doi: 10.1074/jbc.M113.491217. Epub 2013 Dec 30.
- PubMed ID
- 24379400 [ View in PubMed]
- Abstract
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 the destabilization of the ATF5 protein in steady-state conditions and serve as a stabilization domain in the stress response after CdCl2 or NaAsO2 exposure. In this study, we show that interleukin 1beta (IL-1beta), a proinflammatory cytokine, increases 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-1beta response domain. Furthermore, IL-1beta increased the translational efficiency of ATF5 mRNA via the 5' UTRalpha and phosphorylation of the eukaryotic translation initiation factor 2alpha (eIF2alpha). ATF5 knockdown in HepG2 cells up-regulated the IL-1beta-induced expression of the serum amyloid A 1 (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-1beta-mediated immune response and that ATF5 is a negative regulator for IL-1beta-induced expression of SAA1 and SAA2 in HepG2 cells.