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E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I

Gao, W and Chen, Z and Wang, W and Stang, MT (2013) E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I. PLoS ONE, 8 (9).

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Abstract

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation's effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases. © 2013 Gao et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gao, Wgaowent@pitt.eduGAOWENT
Chen, Z
Wang, W
Stang, MT
Date: 4 September 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0073229
Schools and Programs: School of Medicine > Surgery
Refereed: Yes
Date Deposited: 10 Oct 2013 14:35
Last Modified: 05 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/19829

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