Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition.

ABSTRACT: Aggresome formation is a protective cellular response to counteract proteasome dysfunction by sequestering misfolded proteins and reducing proteotoxic stress. Autophagic degradation of the protein aggregates is considered to be a key compensating mechanism for balancing proteostasis. However, the precise role of autophagy in proteasome inhibition-induced aggresome biogenesis remains unclear. Herein, we demonstrate that in the early stage of proteasome inhibition, the maturation of the autophagosome is suppressed, which facilitates aggresome formation of misfolded proteins. Proteasome inhibition-induced phosphorylation of SQSTM1 T269/S272 inhibits its autophagic receptor activity and promotes aggresome formation of misfolded proteins. Inhibiting SQSTM1 T269/S272 phosphorylation using Dorama

SUBMITTER: Zhang C 

PROVIDER: S-EPMC9287315 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature