Mechanistic insight into the regulation of SQSTM1/p62. uri icon

Overview

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.

publication date

  • January 22, 2019

Research

keywords

  • Autophagy

Identity

PubMed Central ID

  • PMC6526835

Scopus Document Identifier

  • 85060632943

Digital Object Identifier (DOI)

  • 10.1080/15548627.2019.1569935

PubMed ID

  • 30653391

Additional Document Info

volume

  • 15

issue

  • 4