PH-dependent regulation of SQSTM1/p62 during autophagy. Issue 1 (2nd January 2019)

• Record Type: Journal Article
• Authors: Kwon, Do Hoon; Kim, Leehyeon; Song, Hyun Kyu
• Is Part Of: Autophagy. Volume 15:Issue 1(2019)
• Page Start: 180
• Page End: 181
• Publication Date: 2019-01-02
• Subjects: Aggrephagy -- autophagy adaptor -- HSPA5/BiP/GRP78 -- N-end rule -- pH-dependent oligomerization -- UBR box; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2018.1532264
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: 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.