Cargando…
The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation
Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfun...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415013/ https://www.ncbi.nlm.nih.gov/pubmed/28298488 http://dx.doi.org/10.1091/mbc.E16-10-0746 |
_version_ | 1783233449483567104 |
---|---|
author | Defenouillère, Quentin Namane, Abdelkader Mouaikel, John Jacquier, Alain Fromont-Racine, Micheline |
author_facet | Defenouillère, Quentin Namane, Abdelkader Mouaikel, John Jacquier, Alain Fromont-Racine, Micheline |
author_sort | Defenouillère, Quentin |
collection | PubMed |
description | Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation. Whereas the steps from stalled 60S recognition to aberrant peptide polyubiquitylation by the RQC complex have been described, the mechanism leading to proteasomal degradation of these defective translation products remains unknown. We show here that the RQC complex also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. In addition, we identify a new partner of this light version of the RQC complex, the E3 ubiquitin ligase Tom1. Tom1 interacts with aberrant nascent peptides and is essential to limit their accumulation and aggregation in the absence of Rqc1; however, its E3 ubiquitin ligase activity is not required. Taken together, these results reveal new roles for Tom1 in protein quality control, aggregate prevention, and, therefore, proteostasis maintenance. |
format | Online Article Text |
id | pubmed-5415013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-54150132017-07-16 The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation Defenouillère, Quentin Namane, Abdelkader Mouaikel, John Jacquier, Alain Fromont-Racine, Micheline Mol Biol Cell Articles Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation. Whereas the steps from stalled 60S recognition to aberrant peptide polyubiquitylation by the RQC complex have been described, the mechanism leading to proteasomal degradation of these defective translation products remains unknown. We show here that the RQC complex also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. In addition, we identify a new partner of this light version of the RQC complex, the E3 ubiquitin ligase Tom1. Tom1 interacts with aberrant nascent peptides and is essential to limit their accumulation and aggregation in the absence of Rqc1; however, its E3 ubiquitin ligase activity is not required. Taken together, these results reveal new roles for Tom1 in protein quality control, aggregate prevention, and, therefore, proteostasis maintenance. The American Society for Cell Biology 2017-05-01 /pmc/articles/PMC5415013/ /pubmed/28298488 http://dx.doi.org/10.1091/mbc.E16-10-0746 Text en © 2017 Defenouillère et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Defenouillère, Quentin Namane, Abdelkader Mouaikel, John Jacquier, Alain Fromont-Racine, Micheline The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title | The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title_full | The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title_fullStr | The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title_full_unstemmed | The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title_short | The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation |
title_sort | ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with tom1 to limit protein aggregation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415013/ https://www.ncbi.nlm.nih.gov/pubmed/28298488 http://dx.doi.org/10.1091/mbc.E16-10-0746 |
work_keys_str_mv | AT defenouillerequentin theribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT namaneabdelkader theribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT mouaikeljohn theribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT jacquieralain theribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT fromontracinemicheline theribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT defenouillerequentin ribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT namaneabdelkader ribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT mouaikeljohn ribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT jacquieralain ribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation AT fromontracinemicheline ribosomeboundqualitycontrolcomplexremainsassociatedtoaberrantpeptidesduringtheirproteasomaltargetingandinteractswithtom1tolimitproteinaggregation |