Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) is a non-redundant E1-like activating enzyme that plays a central role in the two ubiquitin-like conjugation systems required for autophagy. It activates ATG12 for conjugation with ATG5 and facilitates the lipidation of ATG8 family proteins, such as LC3, which is essential for autophagosome membrane expansion and maturation [1, 2]. Beyond its primary role in degradative autophagy, ATG7 also participates in non-canonical processes including LC3-associated phagocytosis, unconventional protein secretion, and the regulation of the cell cycle and apoptosis through direct interaction with the tumor suppressor p53 [2, 13]. In oncology, ATG7 is frequently exploited by tumor cells to survive metabolic and hypoxic stress, leading to the development of small-molecule inhibitors like ATG7-IN-1 and ATG7-IN-2 as potential anti-cancer therapies [10, 11, 16]. However, the therapeutic window for ATG7 inhibition is narrow, as systemic loss of ATG7 activity is associated with severe neurodegeneration, pancreatic dysfunction, and metabolic instability [15, 17]. Conversely, biallelic loss-of-function mutations in the ATG7 gene have been identified as a cause of complex neurodevelopmental disorders in humans, underscoring its vital role in maintaining cellular and tissue homeostasis [15, 19].

Other names

Autophagy-related protein 7ATG12-activating enzyme E1 ATG7APG7APG7LGSA7

Inhibition of the E1-like activating enzyme activity of ATG7, preventing the lipidation of ATG8/LC3 and the conjugation of ATG12 to ATG5, thereby blocking autophagosome formation and the canonical autophagy pathway.