SQSTM1/p62-mediated autophagy compensates for loss of proteasome polyubiquitin recruiting capacity.

ABSTRACT: Protein homeostasis in eukaryotic cells is regulated by 2 highly conserved degradative pathways, the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Recent studies revealed a coordinated and complementary crosstalk between these systems that becomes critical under proteostatic stress. Under physiological conditions, however, the molecular crosstalk between these 2 pathways is still far from clear. Here we describe a cellular model of proteasomal substrate accumulation due to the combined knockdown of PSMD4/S5a and ADRM1, the 2 proteasomal ubiquitin receptors. This model reveals a compensatory autophagic pathway, mediated by a SQSTM1/p62-dependent clearance of accumulated polyubiquitinated proteins. In addition to mediating the sequestration of ubiquitinated cargos into phag

SUBMITTER: Demishtein A 

PROVIDER: S-EPMC5640208 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature