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...

Descripción completa

Detalles Bibliográficos
Autores principales: Defenouillère, Quentin, Namane, Abdelkader, Mouaikel, John, Jacquier, Alain, Fromont-Racine, Micheline
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