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Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides

Eukaryotic cells have evolved multiple mechanisms to detect and eliminate aberrant polypeptides. Co-translational protein surveillance systems play an important role in these mechanisms. These systems include ribosome-associated protein quality control (RQC) that detects aberrant nascent chains stal...

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Autores principales: Ghosh, Arnab, Shcherbik, Natalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554835/
https://www.ncbi.nlm.nih.gov/pubmed/32957466
http://dx.doi.org/10.3390/ijms21186815
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author Ghosh, Arnab
Shcherbik, Natalia
author_facet Ghosh, Arnab
Shcherbik, Natalia
author_sort Ghosh, Arnab
collection PubMed
description Eukaryotic cells have evolved multiple mechanisms to detect and eliminate aberrant polypeptides. Co-translational protein surveillance systems play an important role in these mechanisms. These systems include ribosome-associated protein quality control (RQC) that detects aberrant nascent chains stalled on ribosomes and promotes their ubiquitination and degradation by the proteasome, and ribosome-associated chaperone Ssb/RAC, which ensures correct nascent chain folding. Despite the known function of RQC and Ssb/ribosome-associated complex (RAC) in monitoring the quality of newly generated polypeptides, whether they cooperate during initial stages of protein synthesis remains unexplored. Here, we provide evidence that Ssb/RAC and the ubiquitin ligase Ltn1, the major component of RQC, display genetic and functional cooperativity. Overexpression of Ltn1 rescues growth suppression of the yeast strain-bearing deletions of SSB genes during proteotoxic stress. Moreover, Ssb/RAC promotes Ltn1-dependent ubiquitination of nascent chains associated with 80S ribosomal particles but not with translating ribosomes. Consistent with this finding, quantitative western blot analysis revealed lower levels of Ltn1 associated with 80S ribosomes and with free 60S ribosomal subunits in the absence of Ssb/RAC. We propose a mechanism in which Ssb/RAC facilitates recruitment of Ltn1 to ribosomes, likely by detecting aberrations in nascent chains and leading to their ubiquitination and degradation.
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spelling pubmed-75548352020-10-14 Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides Ghosh, Arnab Shcherbik, Natalia Int J Mol Sci Communication Eukaryotic cells have evolved multiple mechanisms to detect and eliminate aberrant polypeptides. Co-translational protein surveillance systems play an important role in these mechanisms. These systems include ribosome-associated protein quality control (RQC) that detects aberrant nascent chains stalled on ribosomes and promotes their ubiquitination and degradation by the proteasome, and ribosome-associated chaperone Ssb/RAC, which ensures correct nascent chain folding. Despite the known function of RQC and Ssb/ribosome-associated complex (RAC) in monitoring the quality of newly generated polypeptides, whether they cooperate during initial stages of protein synthesis remains unexplored. Here, we provide evidence that Ssb/RAC and the ubiquitin ligase Ltn1, the major component of RQC, display genetic and functional cooperativity. Overexpression of Ltn1 rescues growth suppression of the yeast strain-bearing deletions of SSB genes during proteotoxic stress. Moreover, Ssb/RAC promotes Ltn1-dependent ubiquitination of nascent chains associated with 80S ribosomal particles but not with translating ribosomes. Consistent with this finding, quantitative western blot analysis revealed lower levels of Ltn1 associated with 80S ribosomes and with free 60S ribosomal subunits in the absence of Ssb/RAC. We propose a mechanism in which Ssb/RAC facilitates recruitment of Ltn1 to ribosomes, likely by detecting aberrations in nascent chains and leading to their ubiquitination and degradation. MDPI 2020-09-17 /pmc/articles/PMC7554835/ /pubmed/32957466 http://dx.doi.org/10.3390/ijms21186815 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Ghosh, Arnab
Shcherbik, Natalia
Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title_full Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title_fullStr Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title_full_unstemmed Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title_short Cooperativity between the Ribosome-Associated Chaperone Ssb/RAC and the Ubiquitin Ligase Ltn1 in Ubiquitination of Nascent Polypeptides
title_sort cooperativity between the ribosome-associated chaperone ssb/rac and the ubiquitin ligase ltn1 in ubiquitination of nascent polypeptides
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554835/
https://www.ncbi.nlm.nih.gov/pubmed/32957466
http://dx.doi.org/10.3390/ijms21186815
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