Work

Mechanistic insight into the regulation of SQSTM1/p62

Year: 2019

Type: editorial

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.

Source: Autophagy

DOI: 10.1080/15548627.2019.1569935

Authors: Yi Zhang, Su Ran Mun, Juan F. Linares, Christina G. Towers, Andrew Thorburn, Maria T. Diaz-Meco, Yong Tae Kwon, Tatiana G. Kutateladze

Institutions: University of Colorado Anschutz, Seoul National University, Sanford Burnham Prebys Medical Discovery Institute

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: bronze

Funders: National Research Foundation, Ministry of Science, ICT and Future Planning, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences

Awards: G105882222, G1362092455, G1471725589, G324030696, G4114257425, G4886540993, G5033275444, G5470626986, G6273720688, Role of p62 in metabolic reprograming of the tumor stroma in prostate cancer, Molecular mechanism of chromatin targeting by BRPF1, G8133468353, G8644924125, G9000076191, G9000160334, G9000213455, G9000234130, G9000235595, G972677246

OpenAlex ID: W2909985432

Cites: 1

Cited by: 20

Related to: 10