Proximity labeling reveals dynamic changes in the SQSTM1 protein network

Abstract

ABSTRACTSequestosome1 (SQSTM1) is an autophagy receptor that mediates degrada4on of intracellular cargo, including protein aggregates, through mul4ple protein interac4ons. These interac4ons form the SQSTM1 protein network that are mediated by SQSTM1 func4onal interac4on domains, which include LIR, PB1, UBA and KIR. Despite various abempts to unravel the complexity of the SQSTM1 protein network, our understanding of the rela4onship of various components in cellular physiology and disease states con4nues to evolve. To inves4gate the SQSTM1 protein interac4on network, we performed proximity profile labeling by fusing TurboID with the human protein SQSTM1 (TurboID::SQSTM1). This chimeric protein displayed well-established SQSTM1 features including: produc4on of SQSTM1 intracellular bodies, binding to known SQSTM1 interac4ng partners via defined func4onal SQSTM1 interac4ng domains and capture of novel SQSTM1 interactors. Strikingly, aggregated tau protein altered the protein interac4on network of SQSTM1 to include many stress-associated proteins. Overall, our work reveals the dynamic landscape of the SQSTM1 protein network and offers a resource to study SQSTM1 func4on in cellular physiology and disease state.ProteomeXchange Consor4um PRIDE Submission:Submission details:Project Name: Proximity labeling reveals dynamic changes in the SQSTM1 protein network.Project accession: PXD047725Project DOI: Not applicable