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Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks
Ubiquitination controls the stability or function of many human proteins, thereby regulating a wide range of physiological processes. In most cases the combinatorial pattern of protein interactions that facilitate substrate recognition or modification remain unclear. Moreover, the efficiency of ubiq...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394952/ https://www.ncbi.nlm.nih.gov/pubmed/22493164 http://dx.doi.org/10.1074/mcp.M111.016162 |
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author | Woodsmith, Jonathan Jenn, Robert C. Sanderson, Chris M. |
author_facet | Woodsmith, Jonathan Jenn, Robert C. Sanderson, Chris M. |
author_sort | Woodsmith, Jonathan |
collection | PubMed |
description | Ubiquitination controls the stability or function of many human proteins, thereby regulating a wide range of physiological processes. In most cases the combinatorial pattern of protein interactions that facilitate substrate recognition or modification remain unclear. Moreover, the efficiency of ubiquitination reactions can be altered by the formation of homo- and heterotypic E3-RING complexes. To establish the prevalence and nature of binary E3-RING/E3-RING interactions systematic yeast two-hybrid screens were performed to test 7269 potential interactions between 124 human E3-RING proteins. These studies identified 228 dimeric interactions between 100 E3-RINGs, of which 205 were novel. Complementary co-immunoprecipitation studies were performed to test predicted network interactions, showing a high correlation (64%) with primary yeast two-hybrid data. This data was integrated with known E3-RING interactions, tissue expression profiles and proteomic ubiquitination datasets to facilitate identification of subnetworks in which E3-RING dimerization events have the potential to alter network structure. These results reveal a widespread yet selective pattern of E3-RING dimerization events, which have the potential to confer further combinatorial complexity within human ubiquitination cascades. |
format | Online Article Text |
id | pubmed-3394952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33949522012-07-16 Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks Woodsmith, Jonathan Jenn, Robert C. Sanderson, Chris M. Mol Cell Proteomics Research Ubiquitination controls the stability or function of many human proteins, thereby regulating a wide range of physiological processes. In most cases the combinatorial pattern of protein interactions that facilitate substrate recognition or modification remain unclear. Moreover, the efficiency of ubiquitination reactions can be altered by the formation of homo- and heterotypic E3-RING complexes. To establish the prevalence and nature of binary E3-RING/E3-RING interactions systematic yeast two-hybrid screens were performed to test 7269 potential interactions between 124 human E3-RING proteins. These studies identified 228 dimeric interactions between 100 E3-RINGs, of which 205 were novel. Complementary co-immunoprecipitation studies were performed to test predicted network interactions, showing a high correlation (64%) with primary yeast two-hybrid data. This data was integrated with known E3-RING interactions, tissue expression profiles and proteomic ubiquitination datasets to facilitate identification of subnetworks in which E3-RING dimerization events have the potential to alter network structure. These results reveal a widespread yet selective pattern of E3-RING dimerization events, which have the potential to confer further combinatorial complexity within human ubiquitination cascades. The American Society for Biochemistry and Molecular Biology 2012-07 2012-04-05 /pmc/articles/PMC3394952/ /pubmed/22493164 http://dx.doi.org/10.1074/mcp.M111.016162 Text en © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Research Woodsmith, Jonathan Jenn, Robert C. Sanderson, Chris M. Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title | Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title_full | Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title_fullStr | Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title_full_unstemmed | Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title_short | Systematic Analysis of Dimeric E3-RING Interactions Reveals Increased Combinatorial Complexity in Human Ubiquitination Networks |
title_sort | systematic analysis of dimeric e3-ring interactions reveals increased combinatorial complexity in human ubiquitination networks |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394952/ https://www.ncbi.nlm.nih.gov/pubmed/22493164 http://dx.doi.org/10.1074/mcp.M111.016162 |
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