ZZ-dependent regulation of p62/SQSTM1 in autophagy.

ABSTRACT: Autophagic receptor p62 is a critical mediator of cell detoxification, stress response, and metabolic programs and is commonly deregulated in human diseases. The diverse functions of p62 arise from its ability to interact with a large set of ligands, such as arginylated (Nt-R) substrates. Here, we describe the structural mechanism for selective recognition of Nt-R by the ZZ domain of p62 (p62_ZZ). We show that binding of p62_ZZ to Nt-R substrates stimulates p62 aggregation and macroautophagy and is required for autophagic targeting of p62. p62 is essential for mTORC1 activation in response to arginine, but it is not a direct sensor of free arginine in the mTORC1 pathway. We identified a regulatory linker (RL) region in p62 that binds p62_ZZ in vitro and may mo

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6197226 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature