Autophagy protein 5 (ATG5) (ATG5)

Autophagy protein 5 (ATG5) is a critical mediator of the macroautophagy pathway, primarily responsible for the elongation of the autophagosomal membrane [UniProt, 2024]. It functions as part of a multi-protein complex where it is covalently conjugated to ATG12 and non-covalently bound to ATG16L1; this complex acts as an E3-like ligase to facilitate the lipidation of LC3, a hallmark step in autophagosome formation [Mizushima et al., 2001]. Beyond its core role in nutrient recycling and cellular homeostasis, ATG5 is involved in non-canonical functions such as apoptosis, where its cleavage can promote cell death, and the regulation of immune responses against intracellular pathogens [Ye et al., 2018]. In oncology, ATG5 exhibits a dual role, acting as a tumor suppressor in early stages but facilitating the survival of established tumor cells under metabolic stress [NCBI, 2024]. Therapeutic targeting of ATG5 is being explored to sensitize cancer cells to chemotherapy and to manage inflammatory conditions, though the essential nature of autophagy in healthy tissues presents significant safety challenges [Donohue et al., 2014].

Other names

Autophagy related 5APG5APG5LASPhATG5Autophagy related protein 5

Inhibition of the ATG12-ATG5-ATG16L1 complex formation or activity, thereby preventing LC3 lipidation and autophagosome maturation [Donohue et al., 2014; Liu et al., 2021].