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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...

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Detalles Bibliográficos
Autores principales: Woodsmith, Jonathan, Jenn, Robert C., Sanderson, Chris M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2012
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.
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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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