Atg7 senses ATP levels and regulates AKT₁-PDCD4 phosphorylation-ubiquitination axis to promote survival during metabolic stress.

ABSTRACT: We report that autophagy-related gene 7 (ATG7) modulates p53 activity to regulate cell cycle and survival during metabolic stress, and that indicates Atg7 is functionally involved in cellular homeostasis in autophagy independent fashion. As a protein translation inhibitor, Programmed cell death 4 (PDCD4) expression is regulated by AKT₁ phosphorylation. Here, we find that Atg7 interacts with PDCD4 and AKT₁ to regulate AKT₁-PDCD4 phosphorylation-ubiquitination axis during metabolic stress. We demonstrate that Atg7 senses decrease of ATP levels to suppress AKT-mediated PDCD4 phosphorylation at Ser67, which inhibits PDCD4 ubiquitinating during metabolic stress. Finally, PDCD4 accumulates and functions as a protein translation inhibitor to conserve energy, thus

SUBMITTER: Deng C 

PROVIDER: S-EPMC10713595 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature