title: N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1β (IL-1β)-induced stabilization.
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 1β (IL-1β), 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-1β response domain. Furthermore, IL-1β increased the translational efficiency of ATF5 mRNA via the 5' UTRα and phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). ATF5 knockdown in HepG2 cells up-regulated the IL-1β-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-1β-mediated immune response and that ATF5 is a negative regulator for IL-1β-induced expression of SAA1 and SAA2 in HepG2 cells.
authors.affiliation: From the Laboratory of Environmental Molecular Physiology.
authors.forename: Takanori
authors.initials: T
authors.lastname: Abe
authors.forename: Masaki
authors.initials: M
authors.lastname: Kojima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akanuma
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwashita
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okuyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Umemura
authors.forename: Haruo
authors.initials: H
authors.lastname: Nakano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018053:Arsenites / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D055550:Protein Stability / Q000187:drug effects; D017434:Protein Structure, Tertiary; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000235:genetics; D017670:Sodium Compounds / Q000494:pharmacology
chemical_list: C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D018053:Arsenites; D004791:Enzyme Inhibitors; C508585:IL1B protein, human; D053583:Interleukin-1beta; C521404:SAA1 protein, human; C083772:SAA2 protein, human; D000685:Serum Amyloid A Protein; D017670:Sodium Compounds; C017947:sodium arsenite; D019256:Cadmium Chloride
keywords: Heat Shock Protein; Interleukin; Protein Degradation; Stress Response; Transcription Factors