Processing of autophagic protein LC3 by the 20S proteasome

Zhonghua Gao, Noor Gammoh, Pui Mun Wong, Hediye Erdjument-Bromage, Paul Tempst, Xuejun Jiang

Research output: Contribution to journalArticle

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)126-137
Number of pages12
JournalAutophagy
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Gao, Z., Gammoh, N., Wong, P. M., Erdjument-Bromage, H., Tempst, P., & Jiang, X. (2010). Processing of autophagic protein LC3 by the 20S proteasome. Autophagy, 6(1), 126-137. https://doi.org/10.4161/auto.6.1.10928