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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  1. Paul J Tempst
    324 Tempst
  2. Noor I Gammoh
    8 Gammoh
  3. Xuejun Jiang
    121 Jiang
  4. Pui-Mun Wong
    7 Wong
  5. Zhonghua Gao
    6 Gao