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Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity
Cullin RING ligases (CRLs) are the largest family of cellular E3 ubiquitin ligases and mediate polyubiquitination of a number of cellular substrates. CRLs are activated via the covalent modification of the cullin protein with the ubiquitin-like protein Nedd8. This results in a conformational change...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237615/ https://www.ncbi.nlm.nih.gov/pubmed/22013077 http://dx.doi.org/10.1091/mbc.E11-03-0251 |
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author | Choo, Yin Yin Boh, Boon Kim Lou, Jessica Jie Wei Eng, Jolane Leck, Yee Chin Anders, Benjamin Smith, Peter G. Hagen, Thilo |
author_facet | Choo, Yin Yin Boh, Boon Kim Lou, Jessica Jie Wei Eng, Jolane Leck, Yee Chin Anders, Benjamin Smith, Peter G. Hagen, Thilo |
author_sort | Choo, Yin Yin |
collection | PubMed |
description | Cullin RING ligases (CRLs) are the largest family of cellular E3 ubiquitin ligases and mediate polyubiquitination of a number of cellular substrates. CRLs are activated via the covalent modification of the cullin protein with the ubiquitin-like protein Nedd8. This results in a conformational change in the cullin carboxy terminus that facilitates the ubiquitin transfer onto the substrate. COP9 signalosome (CSN)-mediated cullin deneddylation is essential for CRL activity in vivo. However, the mechanism through which CSN promotes CRL activity in vivo is currently unclear. In this paper, we provide evidence that cullin deneddylation is not intrinsically coupled to substrate polyubiquitination as part of the CRL activation cycle. Furthermore, inhibiting substrate-receptor autoubiquitination is unlikely to account for the major mechanism through which CSN regulates CRL activity. CSN also did not affect recruitment of the substrate-receptor SPOP to Cul3, suggesting it may not function to facilitate the exchange of Cul3 substrate receptors. Our results indicate that CSN binds preferentially to CRLs in the neddylation-induced, active conformation. Binding of the CSN complex to active CRLs may recruit CSN-associated proteins important for CRL regulation. The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle. |
format | Online Article Text |
id | pubmed-3237615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32376152012-03-01 Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity Choo, Yin Yin Boh, Boon Kim Lou, Jessica Jie Wei Eng, Jolane Leck, Yee Chin Anders, Benjamin Smith, Peter G. Hagen, Thilo Mol Biol Cell Articles Cullin RING ligases (CRLs) are the largest family of cellular E3 ubiquitin ligases and mediate polyubiquitination of a number of cellular substrates. CRLs are activated via the covalent modification of the cullin protein with the ubiquitin-like protein Nedd8. This results in a conformational change in the cullin carboxy terminus that facilitates the ubiquitin transfer onto the substrate. COP9 signalosome (CSN)-mediated cullin deneddylation is essential for CRL activity in vivo. However, the mechanism through which CSN promotes CRL activity in vivo is currently unclear. In this paper, we provide evidence that cullin deneddylation is not intrinsically coupled to substrate polyubiquitination as part of the CRL activation cycle. Furthermore, inhibiting substrate-receptor autoubiquitination is unlikely to account for the major mechanism through which CSN regulates CRL activity. CSN also did not affect recruitment of the substrate-receptor SPOP to Cul3, suggesting it may not function to facilitate the exchange of Cul3 substrate receptors. Our results indicate that CSN binds preferentially to CRLs in the neddylation-induced, active conformation. Binding of the CSN complex to active CRLs may recruit CSN-associated proteins important for CRL regulation. The deneddylating activity of CSN would subsequently promote its own dissociation to allow progression through the CRL activation cycle. The American Society for Cell Biology 2011-12-15 /pmc/articles/PMC3237615/ /pubmed/22013077 http://dx.doi.org/10.1091/mbc.E11-03-0251 Text en © 2011 Choo 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 of Cell Biology. |
spellingShingle | Articles Choo, Yin Yin Boh, Boon Kim Lou, Jessica Jie Wei Eng, Jolane Leck, Yee Chin Anders, Benjamin Smith, Peter G. Hagen, Thilo Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title | Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title_full | Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title_fullStr | Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title_full_unstemmed | Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title_short | Characterization of the role of COP9 signalosome in regulating cullin E3 ubiquitin ligase activity |
title_sort | characterization of the role of cop9 signalosome in regulating cullin e3 ubiquitin ligase activity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237615/ https://www.ncbi.nlm.nih.gov/pubmed/22013077 http://dx.doi.org/10.1091/mbc.E11-03-0251 |
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