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A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases

Salicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA’s mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput...

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Autores principales: Choi, Hyong Woo, Wang, Lei, Powell, Adrian F., Strickler, Susan R., Wang, Dekai, Dempsey, D’Maris A., Schroeder, Frank C., Klessig, Daniel F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739329/
https://www.ncbi.nlm.nih.gov/pubmed/31511554
http://dx.doi.org/10.1038/s41598-019-49234-6
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author Choi, Hyong Woo
Wang, Lei
Powell, Adrian F.
Strickler, Susan R.
Wang, Dekai
Dempsey, D’Maris A.
Schroeder, Frank C.
Klessig, Daniel F.
author_facet Choi, Hyong Woo
Wang, Lei
Powell, Adrian F.
Strickler, Susan R.
Wang, Dekai
Dempsey, D’Maris A.
Schroeder, Frank C.
Klessig, Daniel F.
author_sort Choi, Hyong Woo
collection PubMed
description Salicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA’s mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput screen to identify potential SA-binding proteins (SABPs) in human HEK293 cells. Following photo-affinity crosslinking to 4-azidoSA and immuno-selection with an anti-SA antibody, approximately 2,000 proteins were identified. Among these, 95 were enriched more than 10-fold. Pathway enrichment analysis with these 95 candidate SABPs (cSABPs) revealed possible involvement of SA in multiple biological pathways, including (i) glycolysis, (ii) cytoskeletal assembly and/or signaling, and (iii) NF-κB-mediated immune signaling. The two most enriched cSABPs, which corresponded to the glycolytic enzymes alpha-enolase (ENO1) and pyruvate kinase isozyme M2 (PKM2), were assessed for their ability to bind SA and SA’s more potent derivative amorfrutin B1 (amoB1). SA and amoB1 bound recombinant ENO1 and PKM2 at low millimolar and micromolar concentrations, respectively, and inhibited their enzymatic activities in vitro. Consistent with these results, low millimolar concentrations of SA suppressed glycolytic activity in HEK293 cells. To provide insights into how SA might affect various human diseases, a cSABP-human disorder/disease network map was also generated.
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spelling pubmed-67393292019-09-22 A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases Choi, Hyong Woo Wang, Lei Powell, Adrian F. Strickler, Susan R. Wang, Dekai Dempsey, D’Maris A. Schroeder, Frank C. Klessig, Daniel F. Sci Rep Article Salicylic acid (SA) is the major metabolite and active ingredient of aspirin; both compounds reduce pain, fever, and inflammation. Despite over a century of research, aspirin/SA’s mechanism(s) of action is still only partially understood. Here we report the results of a genome-wide, high-throughput screen to identify potential SA-binding proteins (SABPs) in human HEK293 cells. Following photo-affinity crosslinking to 4-azidoSA and immuno-selection with an anti-SA antibody, approximately 2,000 proteins were identified. Among these, 95 were enriched more than 10-fold. Pathway enrichment analysis with these 95 candidate SABPs (cSABPs) revealed possible involvement of SA in multiple biological pathways, including (i) glycolysis, (ii) cytoskeletal assembly and/or signaling, and (iii) NF-κB-mediated immune signaling. The two most enriched cSABPs, which corresponded to the glycolytic enzymes alpha-enolase (ENO1) and pyruvate kinase isozyme M2 (PKM2), were assessed for their ability to bind SA and SA’s more potent derivative amorfrutin B1 (amoB1). SA and amoB1 bound recombinant ENO1 and PKM2 at low millimolar and micromolar concentrations, respectively, and inhibited their enzymatic activities in vitro. Consistent with these results, low millimolar concentrations of SA suppressed glycolytic activity in HEK293 cells. To provide insights into how SA might affect various human diseases, a cSABP-human disorder/disease network map was also generated. Nature Publishing Group UK 2019-09-11 /pmc/articles/PMC6739329/ /pubmed/31511554 http://dx.doi.org/10.1038/s41598-019-49234-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Choi, Hyong Woo
Wang, Lei
Powell, Adrian F.
Strickler, Susan R.
Wang, Dekai
Dempsey, D’Maris A.
Schroeder, Frank C.
Klessig, Daniel F.
A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title_full A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title_fullStr A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title_full_unstemmed A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title_short A genome-wide screen for human salicylic acid (SA)-binding proteins reveals targets through which SA may influence development of various diseases
title_sort genome-wide screen for human salicylic acid (sa)-binding proteins reveals targets through which sa may influence development of various diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739329/
https://www.ncbi.nlm.nih.gov/pubmed/31511554
http://dx.doi.org/10.1038/s41598-019-49234-6
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