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A ubiquitin-like system mediates protein lipidation


Autophagy is a dynamic membrane phenomenon for bulk protein degradation in the lysosome/vacuole1,2. Apg8/Aut7 is an essential factor for autophagy in yeast3,4,5. We previously found that the carboxy-terminal arginine of nascent Apg8 is removed by Apg4/Aut2 protease, leaving a glycine residue at the C terminus6. Apg8 is then converted to a form (Apg8-X) that is tightly bound to the membrane6. Here we report a new mode of protein lipidation. Apg8 is covalently conjugated to phosphatidylethanolamine through an amide bond between the C-terminal glycine and the amino group of phosphatidylethanolamine. This lipidation is mediated by a ubiquitination-like system. Apg8 is a ubiquitin-like protein that is activated by an E1 protein, Apg7 (refs 7, 8), and is transferred subsequently to the E2 enzymes Apg3/Aut1 (ref. 9). Apg7 activates two different ubiquitin-like proteins, Apg12 (ref. 10) and Apg8, and assigns them to specific E2 enzymes, Apg10 (ref. 11) and Apg3, respectively. These reactions are necessary for the formation of Apg8-phosphatidylethanolamine. This lipidation has an essential role in membrane dynamics during autophagy6.

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Figure 1: Characterization of molecule X.
Figure 2: Apg8 is activated by Apg7 (E1 in the Apg12 Ubl system).
Figure 3: Apg3 is a conjugating enzyme (E2) for Apg8.
Figure 4: Apg8 ubiquitination-like system is essential for autophagy.

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We would like to thank D. J. Klionsky for the anti-API antibody, A. Kihara for technical advice, and Jun-ichi Osuga for analysis of fatty acids by GC–MS. This work was supported in part by Grants-in-Aid for the Ministry of Education, Science, Culture and Sports of Japan.

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Correspondence to Yoshinori Ohsumi.

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Ichimura, Y., Kirisako, T., Takao, T. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488–492 (2000).

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