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A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network

E3 ubiquitin ligases (E3s) play a critical role in molecular and cellular mechanisms. However, a large number of E3-substrate interactions (ESIs) remain unrevealed. Here, we integrated the increasing omics data with biological knowledge to characterize and identify ESIs. Multidimensional features we...

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Autores principales: Chen, Di, Liu, Xiaolong, Xia, Tian, Tekcham, Dinesh Singh, Wang, Wen, Chen, Huan, Li, Tongming, Lu, Chang, Ning, Zhen, Liu, Xiumei, Liu, Jing, Qi, Huan, He, Hui, Piao, Hai-long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557761/
https://www.ncbi.nlm.nih.gov/pubmed/31181401
http://dx.doi.org/10.1016/j.isci.2019.05.033
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author Chen, Di
Liu, Xiaolong
Xia, Tian
Tekcham, Dinesh Singh
Wang, Wen
Chen, Huan
Li, Tongming
Lu, Chang
Ning, Zhen
Liu, Xiumei
Liu, Jing
Qi, Huan
He, Hui
Piao, Hai-long
author_facet Chen, Di
Liu, Xiaolong
Xia, Tian
Tekcham, Dinesh Singh
Wang, Wen
Chen, Huan
Li, Tongming
Lu, Chang
Ning, Zhen
Liu, Xiumei
Liu, Jing
Qi, Huan
He, Hui
Piao, Hai-long
author_sort Chen, Di
collection PubMed
description E3 ubiquitin ligases (E3s) play a critical role in molecular and cellular mechanisms. However, a large number of E3-substrate interactions (ESIs) remain unrevealed. Here, we integrated the increasing omics data with biological knowledge to characterize and identify ESIs. Multidimensional features were computed to obtain the association patterns of ESIs, and an ensemble prediction model was constructed to identify ESIs. Comparison with non-ESI cases revealed the specific association patterns of ESIs, which provided meaningful insights into ESI interpretation. Reliability of the prediction model was confirmed from various perspectives. Notably, our evaluations on leucine-rich repeat family of F box (FBXL) family were consistent with a proteomic study, and several substrates for SKP2 and an orphan E3 FBXL6 were experimentally verified. Moreover, a cancer hallmark ESI landscape was studied. Taken together, our study catches a glimpse at the omics-driven ESI association patterns and provides a valuable resource (http://www.esinet.dicp.ac.cn/home.php) to assist ubiquitination research.
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spelling pubmed-65577612019-06-13 A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network Chen, Di Liu, Xiaolong Xia, Tian Tekcham, Dinesh Singh Wang, Wen Chen, Huan Li, Tongming Lu, Chang Ning, Zhen Liu, Xiumei Liu, Jing Qi, Huan He, Hui Piao, Hai-long iScience Article E3 ubiquitin ligases (E3s) play a critical role in molecular and cellular mechanisms. However, a large number of E3-substrate interactions (ESIs) remain unrevealed. Here, we integrated the increasing omics data with biological knowledge to characterize and identify ESIs. Multidimensional features were computed to obtain the association patterns of ESIs, and an ensemble prediction model was constructed to identify ESIs. Comparison with non-ESI cases revealed the specific association patterns of ESIs, which provided meaningful insights into ESI interpretation. Reliability of the prediction model was confirmed from various perspectives. Notably, our evaluations on leucine-rich repeat family of F box (FBXL) family were consistent with a proteomic study, and several substrates for SKP2 and an orphan E3 FBXL6 were experimentally verified. Moreover, a cancer hallmark ESI landscape was studied. Taken together, our study catches a glimpse at the omics-driven ESI association patterns and provides a valuable resource (http://www.esinet.dicp.ac.cn/home.php) to assist ubiquitination research. Elsevier 2019-05-27 /pmc/articles/PMC6557761/ /pubmed/31181401 http://dx.doi.org/10.1016/j.isci.2019.05.033 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Chen, Di
Liu, Xiaolong
Xia, Tian
Tekcham, Dinesh Singh
Wang, Wen
Chen, Huan
Li, Tongming
Lu, Chang
Ning, Zhen
Liu, Xiumei
Liu, Jing
Qi, Huan
He, Hui
Piao, Hai-long
A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title_full A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title_fullStr A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title_full_unstemmed A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title_short A Multidimensional Characterization of E3 Ubiquitin Ligase and Substrate Interaction Network
title_sort multidimensional characterization of e3 ubiquitin ligase and substrate interaction network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557761/
https://www.ncbi.nlm.nih.gov/pubmed/31181401
http://dx.doi.org/10.1016/j.isci.2019.05.033
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