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Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration

Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identif...

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Autores principales: Uzoma, Ijeoma, Hu, Jianfei, Cox, Eric, Xia, Shuli, Zhou, Jianying, Rho, Hee-Sool, Guzzo, Catherine, Paul, Corry, Ajala, Olutobi, Goodwin, C. Rory, Jeong, Junseop, Moore, Cedric, Zhang, Hui, Meluh, Pamela, Blackshaw, Seth, Matunis, Michael, Qian, Jiang, Zhu, Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930406/
https://www.ncbi.nlm.nih.gov/pubmed/29438996
http://dx.doi.org/10.1074/mcp.RA117.000014
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author Uzoma, Ijeoma
Hu, Jianfei
Cox, Eric
Xia, Shuli
Zhou, Jianying
Rho, Hee-Sool
Guzzo, Catherine
Paul, Corry
Ajala, Olutobi
Goodwin, C. Rory
Jeong, Junseop
Moore, Cedric
Zhang, Hui
Meluh, Pamela
Blackshaw, Seth
Matunis, Michael
Qian, Jiang
Zhu, Heng
author_facet Uzoma, Ijeoma
Hu, Jianfei
Cox, Eric
Xia, Shuli
Zhou, Jianying
Rho, Hee-Sool
Guzzo, Catherine
Paul, Corry
Ajala, Olutobi
Goodwin, C. Rory
Jeong, Junseop
Moore, Cedric
Zhang, Hui
Meluh, Pamela
Blackshaw, Seth
Matunis, Michael
Qian, Jiang
Zhu, Heng
author_sort Uzoma, Ijeoma
collection PubMed
description Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identified over 2500 proteins that undergo SUMO E3-dependent SUMOylation. We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between phosphorylation and SUMOylation. Cell-based analyses of tyrosine kinase, PYK2, revealed that SUMOylation at four lysine residues promoted PYK2 autophosphorylation at tyrosine 402, which in turn enhanced its interaction with SRC and full activation of the SRC-PYK2 complex. SUMOylation on WT but not the 4KR mutant of PYK2 further elevated phosphorylation of the downstream components in the focal adhesion pathway, such as paxillin and Erk1/2, leading to significantly enhanced cell migration during wound healing. These studies illustrate how our SUMO E3 ligase-substrate network can be used to explore crosstalk between SUMOylation and other PTMs in many biological processes.
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spelling pubmed-59304062018-05-03 Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration Uzoma, Ijeoma Hu, Jianfei Cox, Eric Xia, Shuli Zhou, Jianying Rho, Hee-Sool Guzzo, Catherine Paul, Corry Ajala, Olutobi Goodwin, C. Rory Jeong, Junseop Moore, Cedric Zhang, Hui Meluh, Pamela Blackshaw, Seth Matunis, Michael Qian, Jiang Zhu, Heng Mol Cell Proteomics Research Proteomics studies have revealed that SUMOylation is a widely used post-translational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown. Using a human proteome microarray-based activity screen, we identified over 2500 proteins that undergo SUMO E3-dependent SUMOylation. We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between phosphorylation and SUMOylation. Cell-based analyses of tyrosine kinase, PYK2, revealed that SUMOylation at four lysine residues promoted PYK2 autophosphorylation at tyrosine 402, which in turn enhanced its interaction with SRC and full activation of the SRC-PYK2 complex. SUMOylation on WT but not the 4KR mutant of PYK2 further elevated phosphorylation of the downstream components in the focal adhesion pathway, such as paxillin and Erk1/2, leading to significantly enhanced cell migration during wound healing. These studies illustrate how our SUMO E3 ligase-substrate network can be used to explore crosstalk between SUMOylation and other PTMs in many biological processes. The American Society for Biochemistry and Molecular Biology 2018-05 2018-02-08 /pmc/articles/PMC5930406/ /pubmed/29438996 http://dx.doi.org/10.1074/mcp.RA117.000014 Text en © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Research
Uzoma, Ijeoma
Hu, Jianfei
Cox, Eric
Xia, Shuli
Zhou, Jianying
Rho, Hee-Sool
Guzzo, Catherine
Paul, Corry
Ajala, Olutobi
Goodwin, C. Rory
Jeong, Junseop
Moore, Cedric
Zhang, Hui
Meluh, Pamela
Blackshaw, Seth
Matunis, Michael
Qian, Jiang
Zhu, Heng
Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title_full Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title_fullStr Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title_full_unstemmed Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title_short Global Identification of Small Ubiquitin-related Modifier (SUMO) Substrates Reveals Crosstalk between SUMOylation and Phosphorylation Promotes Cell Migration
title_sort global identification of small ubiquitin-related modifier (sumo) substrates reveals crosstalk between sumoylation and phosphorylation promotes cell migration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930406/
https://www.ncbi.nlm.nih.gov/pubmed/29438996
http://dx.doi.org/10.1074/mcp.RA117.000014
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