Processing of autophagic protein LC3 by the 20S proteasome Journal Article
| Authors: | Gao, Z.; Gammoh, N.; Wong, P. M.; Erdjument-Bromage, H.; Tempst, P.; Jiang, X. |
| Article Title: | Processing of autophagic protein LC3 by the 20S proteasome |
| Abstract: | Ubiquitin-proteasome system and autophagy are the two major mechanisms for protein degradation in eukaryotic cells. LC3, a ubiquitin-like protein, plays an essential role in autophagy through its ability to be conjugated to phosphatidylethanolamine. In this study, we discovered a novel LC3-processing activity, and biochemically purified the 20s proteasome as the responsible enzyme. Processing of LC3 by the 20s proteasome is ATP- and ubiquitin- independent, and requires both the N-terminal helices and the ubiquitin fold of LC3; addition of the N-terminal helices of LC3 to the N terminus of ubiquitin renders ubiquitin susceptible to 20s proteasomal activity. Further, the 20s proteasome processes LC3 in a stepwise manner, it first cleaves LC3 within its ubiquitin fold and thus disrupts the conjugation function of LC3; subsequently and especially at high concentrations of the proteasome, LC3 is completely degraded. Intriguingly, proteolysis of LC3 by the 20s proteasome can be inhibited by p62, an LC3-binding protein that mediates autophagic degradation of polyubiquitin aggregates in cells. Therefore, our study implicates a potential mechanism underlying interplay between the proteasomal and autophagic pathways. This study also provides biochemical evidence suggesting relevance of the controversial ubiquitin-independent proteolytic activity of the 20s proteasome. © 2010 Landes Bioscience. |
| Keywords: | unclassified drug; human cell; nonhuman; ubiquitin; protein function; animal cell; mouse; animals; mice; cells, cultured; proteasome; proteasome endopeptidase complex; protein degradation; cell protein; protein binding; enzyme activity; cysteine proteinase inhibitors; hela cells; protein processing; ubiquitination; protein processing, post-translational; hybrid protein; amino terminal sequence; eukaryota; substrate specificity; adaptor proteins, signal transducing; binding protein; protein structure, tertiary; molecular interaction; catalysis; protein folding; molecular biology; autophagy; concentration (parameters); polyubiquitin; 20s proteasome; protein cleavage; enzyme mechanism; cell extracts; protein p62; conjugation; lc3; p62; cell extract; protein lc3; leupeptins; microtubule-associated proteins |
| Journal Title: | Autophagy |
| Volume: | 6 |
| Issue: | 1 |
| ISSN: | 1554-8627 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2010-01-01 |
| Start Page: | 126 |
| End Page: | 137 |
| Language: | English |
| DOI: | 10.4161/auto.6.1.10928 |
| PUBMED: | 20061800 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "Source: Scopus" |
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