Mechanistic insight into the regulation of SQSTM1/p62. Issue 4 (3rd April 2019)

• Record Type: Journal Article
• Authors: Zhang, Yi; Mun, Su Ran; Linares, Juan F.; Towers, Christina G.; Thorburn, Andrew; Diaz-Meco, Maria T.; Kwon, Yong Tae; Kutateladze, Tatiana G.
• Is Part Of: Autophagy. Volume 15:Issue 4(2019)
• Page Start: 735
• Page End: 737
• Publication Date: 2019-04-03
• Subjects: Arginylated substrates -- autoregulation -- macroautophagy -- p62 -- ZZ domain; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2019.1569935
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: SQSTM1/p62 facilitates responses to various cellular stresses and has been implicated in human diseases. This protein functions as a major cytoplasmic signaling hub and has multiple binding partners, including arginylated (Nt-R) proteins that are recognized by the ZZ domain of SQSTM1/p62 (SQSTM1/p62ZZ ). We have determined the molecular mechanism of Nt-R recognition using a combination of biochemical and NMR approaches and obtained the crystal structure of SQSTM1/p62ZZ in complex with Nt-R. We found that binding of SQSTM1/p62ZZ to Nt-R induces SQSTM1/p62 puncta formation and macroautophagy/autophagy and identified a regulatory linker (RL) region of SQSTM1/p62 that associates with SQSTM1/p62ZZ in vitro . Our findings suggest a mechanism for SQSTM1/p62 autoregulation that can be essential in mediating autophagy.