N-terminal Hydrophobic Amino Acids of Activating Transcription Factor 5 (ATF5) Protein Confer Interleukin 1β (IL-1β)-induced Stabilization

Abstract

Background:The N-terminal region of ATF5 is responsible for its CdCl 2 -and NaAsO 2 -induced expression. Results: IL-1␤ stabilizes ATF5 protein and elevates the translation efficiency of ATF5 mRNA. Conclusion:The N-terminal hydrophobic amino acids of ATF5 are important for protein stabilization and responsiveness to IL-1␤. Significance: This study provides new insights about the roles of ATF5 in immune response.

Stabilization of ATF5 by TAK1–Nemo-Like Kinase Critically Regulates the Interleukin-1β-Stimulated C/EBP Signaling Pathway

“…Recently, it has been demonstrated that the N-terminal amino acids of ATF5 are important for IL-1␤-induced ATF5 stabilization, which is mainly controlled by proteasome-mediated proteolysis (31). Similarly, in our experiments, we found that the N-terminal residues of ATF5 conferred NLK-induced stabilization, which was significantly blocked by proteasome inhibition.…”

“…The asterisks indicate a significant difference (P Ͻ 0.05) calculated by one-way analysis of variance followed by Tukey's multiple-comparison test. (31). Accordingly, truncated ATF5 was overexpressed with NLK to determine whether the N-terminal residues were required for the NLK-mediated stabilization of ATF5.…”

“…ATF5 was first identified as a partner of C/EBP␥ (26), and a recent study demonstrated that ATF5 associates with C/EBP␤ during 3T3-L1 differentiation (27). Several reports have suggested that ATF5 is inherently very unstable; however, it can be stabilized in response to a variety of stimuli, such as cisplatin (28), cadmium chloride (CdCl 2 ) (29), sodium arsenite (NaAsO 2 ) (30), and IL-1␤ (31).…”

N-Terminal Amino Acids Determine KLF4 Protein Stability in 2A Peptide-Linked Polycistronic Reprogramming Constructs

“…Expression of transgenes was induced with dox 24 h after transfection of MEFs and protein expression was detected after 48 h by western blot analysis. Consistent with expression in HEK293T cells ( Figure 1A) Hydrophobic N-Terminal Non-native Amino Acids Cause Proteasomal Degradation of KLF4 S Because a hydrophobic N-terminus can impair protein stability (Abe et al, 2014), we evaluated the hydrophobicity of the N-terminus for each KLF4 variant ( Figures S2A and S2B). The first nine N-terminal amino acids of KLF4 L encode mostly hydrophilic residues, while the N-terminus of KLF4 S was found to be mainly hydrophobic ( Figure S2A, right).…”

“…In the P-N-end rule, [P] and also penultimate residues are involved in recruitment of the GID ubiquitin ligase subunit GID4, while adjacent [E] residues are prone to escape from the recognition (Chen et al, 2017). The principle of these rules is still not fully understood, but hydrophobicity of N-terminal residues is one of the regulatory factors in the protein stability (Abe et al, 2014). Consistent with these previous reports, we found an enhanced hydrophobicity at the N-terminus of KLF4 S suggesting that addition of [P] and [PL] triggers its proteasomal degradation.…”