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SGTA regulates the cytosolic quality control of hydrophobic substrates
Hydrophobic amino acids are normally shielded from the cytosol and their exposure is often used as an indicator of protein misfolding to enable the chaperone-mediated recognition and quality control of aberrant polypeptides. Mislocalised membrane proteins (MLPs) represent a particular challenge to c...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215715/ https://www.ncbi.nlm.nih.gov/pubmed/25179605 http://dx.doi.org/10.1242/jcs.155648 |
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author | Wunderley, Lydia Leznicki, Pawel Payapilly, Aishwarya High, Stephen |
author_facet | Wunderley, Lydia Leznicki, Pawel Payapilly, Aishwarya High, Stephen |
author_sort | Wunderley, Lydia |
collection | PubMed |
description | Hydrophobic amino acids are normally shielded from the cytosol and their exposure is often used as an indicator of protein misfolding to enable the chaperone-mediated recognition and quality control of aberrant polypeptides. Mislocalised membrane proteins (MLPs) represent a particular challenge to cellular quality control, and, in this study, membrane protein fragments have been exploited to study a specialised pathway that underlies the efficient detection and proteasomal degradation of MLPs. Our data show that the BAG6 complex and SGTA compete for cytosolic MLPs by recognition of their exposed hydrophobicity, and the data suggest that SGTA acts to maintain these substrates in a non-ubiquitylated state. Hence, SGTA might counter the actions of BAG6 to delay the ubiquitylation of specific precursors and thereby increase their opportunity for successful post-translational delivery to the endoplasmic reticulum. However, when SGTA is overexpressed, the normally efficient removal of aberrant MLPs is delayed, increasing their steady-state level and promoting aggregation. Our data suggest that SGTA regulates the cellular fate of a range of hydrophobic polypeptides should they become exposed to the cytosol. |
format | Online Article Text |
id | pubmed-4215715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-42157152014-11-17 SGTA regulates the cytosolic quality control of hydrophobic substrates Wunderley, Lydia Leznicki, Pawel Payapilly, Aishwarya High, Stephen J Cell Sci Research Article Hydrophobic amino acids are normally shielded from the cytosol and their exposure is often used as an indicator of protein misfolding to enable the chaperone-mediated recognition and quality control of aberrant polypeptides. Mislocalised membrane proteins (MLPs) represent a particular challenge to cellular quality control, and, in this study, membrane protein fragments have been exploited to study a specialised pathway that underlies the efficient detection and proteasomal degradation of MLPs. Our data show that the BAG6 complex and SGTA compete for cytosolic MLPs by recognition of their exposed hydrophobicity, and the data suggest that SGTA acts to maintain these substrates in a non-ubiquitylated state. Hence, SGTA might counter the actions of BAG6 to delay the ubiquitylation of specific precursors and thereby increase their opportunity for successful post-translational delivery to the endoplasmic reticulum. However, when SGTA is overexpressed, the normally efficient removal of aberrant MLPs is delayed, increasing their steady-state level and promoting aggregation. Our data suggest that SGTA regulates the cellular fate of a range of hydrophobic polypeptides should they become exposed to the cytosol. The Company of Biologists 2014-11-01 /pmc/articles/PMC4215715/ /pubmed/25179605 http://dx.doi.org/10.1242/jcs.155648 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Wunderley, Lydia Leznicki, Pawel Payapilly, Aishwarya High, Stephen SGTA regulates the cytosolic quality control of hydrophobic substrates |
title | SGTA regulates the cytosolic quality control of hydrophobic substrates |
title_full | SGTA regulates the cytosolic quality control of hydrophobic substrates |
title_fullStr | SGTA regulates the cytosolic quality control of hydrophobic substrates |
title_full_unstemmed | SGTA regulates the cytosolic quality control of hydrophobic substrates |
title_short | SGTA regulates the cytosolic quality control of hydrophobic substrates |
title_sort | sgta regulates the cytosolic quality control of hydrophobic substrates |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215715/ https://www.ncbi.nlm.nih.gov/pubmed/25179605 http://dx.doi.org/10.1242/jcs.155648 |
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