Shintani, T. et al. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J. 18, 5234-5241

Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
The EMBO Journal (Impact Factor: 10.43). 11/1999; 18(19):5234-41. DOI: 10.1093/emboj/18.19.5234
Source: PubMed


Autophagy is a cellular process for bulk degradation of cytoplasmic components. The attachment of Apg12p, a modifier with no significant similarity to ubiquitin, to Apg5p is crucial for autophagy in yeast. This reaction proceeds in a ubiquitination-like manner, and requires Apg7p and Apg10p. Apg7p exhibits a considerable similarity to ubiquitin-activating enzyme (E1) and is found to activate Apg12p with ATP hydrolysis. Apg10p, on the other hand, shows no significant similarity to other proteins whose functions are known. Here, we show that after activation by Apg7p, Apg12p is transferred to the Cys-133 residue of Apg10p to form an Apg12p-Apg10p thioester. Cells expressing Apg10p(C133S) do not generate the Apg12p-Apg5p conjugate, which leads to defects in autophagy and cytoplasm-to-vacuole targeting of aminopeptidase I. These findings indicate that Apg10p is a new type of protein-conjugating enzyme that functions in the Apg12p-Apg5p conjugation pathway.

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    • "In this system, the C-terminal glycine of Atg12 is covalently attached to Atg5 through an internal lysine residue. This process requires the action of Atg7 (E1 enzyme) [88] and Atg10 (E2 enzyme) ([89]. A third protein, Atg16, binds to the Atg5 component of the Atg12-Atg5 conjugate and dimerizes to link a pair of Atg12-Atg5 conjugates. "
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    • "Autophagy is a genetically programmed, evolutionarily conserved process coordinated by a family of genes, called Atg, that lead to the degradation of organelles and proteins. It involves the formation of double-membrane vesicles, containing cellular components, that merge to lysosomes, forming the autophagolysosome, where the components are degraded and the products generated are reused by the cell [40], [41]. In this view, autophagy acts as a prosurvival mechanism, mainly in adverse conditions such as nutrient and oxygen deprivation. "
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    • "The vesicle elongation and completion process requires two ubiquitin-like pathways involving two ubiquitin-like proteins, Atg12 and Atg8 proteins, respectively. The first pathway includes an Atg12-Atg5 covalently conjugating system, and subsequently the formation of which requires an E1- and E2- like proteins Atg7 and Atg10, respectively21, 22, 23. In mouse, the Atg12-Atg5 conjugate interacts with a small coiled-coil protein, Atg16L (an ortholog of Atg 16 in yeast), to form an Atg12-Atg5-Atg16L complex. "
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