Reprogramming endo-lysosomal proteostasis disease stress by UBR1- and arginylation-driven endophagy and autophagy protein quality control
| dc.contributor.author | Wang, B.B. | |
| dc.contributor.author | Apaja, P.M. | |
| dc.date.issued | 2022 | |
| dc.description.abstract | Protein quality control (PQC) is a conformational surveillance system critical to maintaining native protein composition in the cell. However, PQC mechanisms at the endo-lysosomal pathway especially toward membrane proteins and during cumulative endo-lysosomal stress are incompletely understood. We recently identified the ubiquitin ligase UBR1 as a PQC E3 ubiquitin-ligase for endosomal and/or cytosolic Ca²⁺-increase mediated proteostasis disease stress. As a consequence of the endosomal stress and/or cytosolic Ca²⁺-increase, the QC pathway using selective endosomal autophagy (endophagy) and autophagy was activated for ubiquitinated and arginylated UBR1-SQSTM1/p62 cargoes. In turn, the loss of UBR1, arginylation or both evoke endo-lysosomal pathway stress. Our data suggest that UBR1 with arginylation-dependent endophagy and autophagy is required during proteostasis perturbations and highlight the importance of UBR1 in stressinduced autophagy QC with implications for various human diseases. | |
| dc.description.statementofresponsibility | Ben B. Wanga, and Pirjo M. Apaja | |
| dc.identifier.citation | Autophagy Reports, 2022; 1(1):260-263 | |
| dc.identifier.doi | 10.1080/27694127.2022.2097274 | |
| dc.identifier.issn | 2769-4127 | |
| dc.identifier.issn | 2769-4127 | |
| dc.identifier.orcid | Apaja, P.M. [0000-0002-1622-2332] | |
| dc.identifier.uri | https://hdl.handle.net/2440/146197 | |
| dc.language.iso | en | |
| dc.publisher | Informa UK Limited | |
| dc.rights | © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. | |
| dc.source.uri | https://doi.org/10.1080/27694127.2022.2097274 | |
| dc.subject | autophagosome; endosome; lysosome; proteostasis stress; regeneration; SQSTM1/p62; ubiquitination | |
| dc.title | Reprogramming endo-lysosomal proteostasis disease stress by UBR1- and arginylation-driven endophagy and autophagy protein quality control | |
| dc.type | Journal article | |
| pubs.publication-status | Published online |