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Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1
Proteasome-mediated substrate degradation is an essential process that relies on the coordinated actions of ubiquitin (Ub), shuttle proteins containing Ub-like (UBL) domains, and the proteasome. Proteinaceous substrates are tagged with polyUb and shuttle proteins, and these signals are then recogniz...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008175/ https://www.ncbi.nlm.nih.gov/pubmed/33617881 http://dx.doi.org/10.1016/j.jbc.2021.100450 |
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author | Boughton, Andrew J. Zhang, Daoning Singh, Rajesh K. Fushman, David |
author_facet | Boughton, Andrew J. Zhang, Daoning Singh, Rajesh K. Fushman, David |
author_sort | Boughton, Andrew J. |
collection | PubMed |
description | Proteasome-mediated substrate degradation is an essential process that relies on the coordinated actions of ubiquitin (Ub), shuttle proteins containing Ub-like (UBL) domains, and the proteasome. Proteinaceous substrates are tagged with polyUb and shuttle proteins, and these signals are then recognized by the proteasome, which subsequently degrades the substrate. To date, three proteasomal receptors have been identified, as well as multiple shuttle proteins and numerous types of polyUb chains that signal for degradation. While the components of this pathway are well-known, our understanding of their interplay is unclear—especially in the context of Rpn1, the largest proteasomal subunit. Here, using nuclear magnetic resonance (NMR) spectroscopy in combination with competition assays, we show that Rpn1 associates with UBL-containing proteins and polyUb chains, while exhibiting a preference for shuttle protein Rad23. Rpn1 appears to contain multiple Ub/UBL-binding sites, theoretically as many as one for each of its hallmark proteasome/cyclosome repeats. Remarkably, we also find that binding sites on Rpn1 can be shared among Ub and UBL species, while proteasomal receptors Rpn1 and Rpn10 can compete with each other for binding of shuttle protein Dsk2. Taken together, our results rule out the possibility of exclusive recognition sites on Rpn1 for individual Ub/UBL signals and further emphasize the complexity of the redundancy-laden proteasomal degradation pathway. |
format | Online Article Text |
id | pubmed-8008175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80081752021-04-02 Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 Boughton, Andrew J. Zhang, Daoning Singh, Rajesh K. Fushman, David J Biol Chem Research Article Proteasome-mediated substrate degradation is an essential process that relies on the coordinated actions of ubiquitin (Ub), shuttle proteins containing Ub-like (UBL) domains, and the proteasome. Proteinaceous substrates are tagged with polyUb and shuttle proteins, and these signals are then recognized by the proteasome, which subsequently degrades the substrate. To date, three proteasomal receptors have been identified, as well as multiple shuttle proteins and numerous types of polyUb chains that signal for degradation. While the components of this pathway are well-known, our understanding of their interplay is unclear—especially in the context of Rpn1, the largest proteasomal subunit. Here, using nuclear magnetic resonance (NMR) spectroscopy in combination with competition assays, we show that Rpn1 associates with UBL-containing proteins and polyUb chains, while exhibiting a preference for shuttle protein Rad23. Rpn1 appears to contain multiple Ub/UBL-binding sites, theoretically as many as one for each of its hallmark proteasome/cyclosome repeats. Remarkably, we also find that binding sites on Rpn1 can be shared among Ub and UBL species, while proteasomal receptors Rpn1 and Rpn10 can compete with each other for binding of shuttle protein Dsk2. Taken together, our results rule out the possibility of exclusive recognition sites on Rpn1 for individual Ub/UBL signals and further emphasize the complexity of the redundancy-laden proteasomal degradation pathway. American Society for Biochemistry and Molecular Biology 2021-02-20 /pmc/articles/PMC8008175/ /pubmed/33617881 http://dx.doi.org/10.1016/j.jbc.2021.100450 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Boughton, Andrew J. Zhang, Daoning Singh, Rajesh K. Fushman, David Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title | Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title_full | Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title_fullStr | Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title_full_unstemmed | Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title_short | Polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit Rpn1 |
title_sort | polyubiquitin and ubiquitin-like signals share common recognition sites on proteasomal subunit rpn1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008175/ https://www.ncbi.nlm.nih.gov/pubmed/33617881 http://dx.doi.org/10.1016/j.jbc.2021.100450 |
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