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

63 Citations (Scopus)

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

Fingerprint

Proteasome Endopeptidase Complex
Ubiquitin
Proteins
Autophagy
Proteolysis
Ubiquitins
Polyubiquitin
Eukaryotic Cells
Carrier Proteins
Adenosine Triphosphate
Enzymes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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
Gao, Zhonghua ; Gammoh, Noor ; Wong, Pui Mun ; Erdjument-Bromage, Hediye ; Tempst, Paul ; Jiang, Xuejun. / Processing of autophagic protein LC3 by the 20S proteasome. In: Autophagy. 2010 ; Vol. 6, No. 1. pp. 126-137.
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Gao, Z, Gammoh, N, Wong, PM, Erdjument-Bromage, H, Tempst, P & Jiang, X 2010, 'Processing of autophagic protein LC3 by the 20S proteasome', Autophagy, vol. 6, no. 1, pp. 126-137. https://doi.org/10.4161/auto.6.1.10928

Processing of autophagic protein LC3 by the 20S proteasome. / Gao, Zhonghua; Gammoh, Noor; Wong, Pui Mun; Erdjument-Bromage, Hediye; Tempst, Paul; Jiang, Xuejun.

In: Autophagy, Vol. 6, No. 1, 01.01.2010, p. 126-137.

Research output: Contribution to journalArticle

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