pH-dependent regulation of SQSTM1/p62 during autophagy

Do Hoon Kwon, Leehyeon Kim, Hyun Kyu Song

Research output: Contribution to journalComment/debatepeer-review

13 Citations (Scopus)


During macroautophagy/autophagy, SQSTM1/p62 plays dual roles as a key mediator of cargo selection and as an autophagic substrate. SQSTM1 links N-degrons and/or ubiquitinated cargoes to the autophagosome by forming homo- or hetero-oligomers, although its N-degron recognition and oligomerization mechanisms are not well characterized. We recently found that SQSTM1 is a novel type of N-recognin whose ZZ domain provides a negatively-charged binding pocket for Arg-charged N-degron (Nt-Arg), a prototype type-1 substrate. Although differences in binding affinity exist for each N-degron, SQSTM1 also interacts with type-2 N-degrons, such as Nt-Tyr and Nt-Trp. Intriguingly, interactions between SQSTM1’s ZZ domain and various N-degrons are greatly influenced by pH-dependent SQSTM1 oligomerization via its PB1 domain. Because cellular pH conditions vary from neutral to acidic depending on the stage of autophagy, the pH-dependent regulation of SQSTM1’s oligomerization must be tightly coupled with the autophagic process.

Original languageEnglish
Pages (from-to)180-181
Number of pages2
Issue number1
Publication statusPublished - 2019 Jan 2

Bibliographical note

Funding Information:
This work was supported by National Research Foundation grants from the Korean government (NRF-2016R1E1A1A01942623 and BRL: No. 2015041919). L.K. is a recipient of a POSCO Science Fellowship of POSCO TJ Park Foundation.

Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.


  • Aggrephagy
  • HSPA5/BiP/GRP78
  • N-end rule
  • UBR box
  • autophagy adaptor
  • pH-dependent oligomerization

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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