Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter

Do Hoon Kwon, Ok Hyun Park, Leehyeon Kim, Yang Ouk Jung, Yeonkyoung Park, Hyeongseop Jeong, Jaekyung Hyun, Yoon Ki Kim, Hyun Kyu Song

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

p62/SQSTM1 is the key autophagy adapter protein and the hub of multi-cellular signaling. It was recently reported that autophagy and N-end rule pathways are linked via p62. However, the exact recognition mode of degrading substrates and regulation of p62 in the autophagic pathway remain unknown. Here, we present the complex structures between the ZZ-domain of p62 and various type-1 and type-2 N-degrons. The binding mode employed in the interaction of the ZZ-domain with N-degrons differs from that employed by classic N-recognins. It was also determined that oligomerization via the PB1 domain can control functional affinity to the R-BiP substrate. Unexpectedly, we found that self-oligomerization and disassembly of p62 are pH-dependent. These findings broaden our understanding of the functional repertoire of the N-end rule pathway and provide an insight into the regulation of p62 during the autophagic pathway.

Original languageEnglish
Article number3291
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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adapters
Oligomerization
Autophagy
degradation
Cell signaling
Degradation
Substrates
hubs
affinity
proteins
Proteins
interactions
recognins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter. / Kwon, Do Hoon; Park, Ok Hyun; Kim, Leehyeon; Jung, Yang Ouk; Park, Yeonkyoung; Jeong, Hyeongseop; Hyun, Jaekyung; Kim, Yoon Ki; Song, Hyun Kyu.

In: Nature Communications, Vol. 9, No. 1, 3291, 01.12.2018.

Research output: Contribution to journalArticle

Kwon, Do Hoon ; Park, Ok Hyun ; Kim, Leehyeon ; Jung, Yang Ouk ; Park, Yeonkyoung ; Jeong, Hyeongseop ; Hyun, Jaekyung ; Kim, Yoon Ki ; Song, Hyun Kyu. / Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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