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Title 

p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis

Authors 

Hyunjoo Cha-MolstadJi-Eun YuZ FengS H LeeJung Gi KimP YangB HanK W SungY D YooJoonsung HwangT McGuireS M ShimH D SongS GanipisettiN WangJ M JangM J LeeSeung Jun KimKyung Ho LeeJ T HongA CiechanoverI Mook-JungK P KimX Q XieY T KwonBo Yeon Kim

Publisher 

Nature Publishing Group

Issue Date 

2017

Citation 

Nature Communications

Abstract 

Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons

ISSN 

2041-1723

Link 

http://dx.doi.org/10.1038/s41467-017-00085-7

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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