Background
The enzymes of the autophagy pathway play a pivotal role in the degradation of cytoplasmic constituents and organelles. Structures known as autophagosomes sequester portions of the cytoplasm which are degraded by the lysosome and recycled back into the cell (Kuma et al. 2004). Three classes of enzymes are involved in autophagy; E1-like activating enzymes, E2-like conjugating enzymes and E3-like ligases. Ubiquitin-like proteins (ubl) Autophagy 12 (ATG12) and ATG8 are activated by ATG7 the E1-like activating enzyme. ATG12 and ATG8 are transferred to two E2-like conjugating enzymes ATG10 and ATG3 respectively. Cloning of the human ATG7 gene was first described by Yuan et al. (1999) and ATG7 shares 38% sequence identity to its yeast homologue Apg7. ATG7 can also activate ATG8 mammalian homologues, GABARAP and GATE-16. It forms a homodimer via the C-terminal region that is important for enzyme substrate interaction and E1-E2 complex formation (Komatsu et al. 2005). ATG7DFAP a mutant form of the ATG7 E1-like activating enzyme which lacks the (Phe-Asp-Pro) FAP motif has been shown to be unable to form an E2 substrate intermediate with ATG3 and the ubl Microtubule-Associated Protein 1, Light Chain 3 (MAPLC3) (Tanida et al. 2012). ATG7 has been shown to be involved in a novel pathway in which the inhibition of caspase-8 results in autophagic death induced by receptor-interacting protein (RIP), Jun amino-terminal kinase, and beclin-1 (Yu et al. 2004).
References
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