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Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization
Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity‐based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518382/ https://www.ncbi.nlm.nih.gov/pubmed/34388301 http://dx.doi.org/10.1002/anie.202106968 |
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author | Chen, Deng Xiao, Zhangping Guo, Hao Gogishvili, Dea Setroikromo, Rita van der Wouden, Petra E. Dekker, Frank J. |
author_facet | Chen, Deng Xiao, Zhangping Guo, Hao Gogishvili, Dea Setroikromo, Rita van der Wouden, Petra E. Dekker, Frank J. |
author_sort | Chen, Deng |
collection | PubMed |
description | Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity‐based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed Labelox B as a potent covalent LOX inhibitor for one‐step activity‐based labeling of proteins with LOX activity. Labelox B was used to establish an ELISA‐based assay for affinity capture and antibody‐based detection of specific LOX isoenzymes. Moreover, Labelox B enabled efficient activity‐based labeling of endogenous LOXs in living cells. LOX proved to localize in the nucleus, which was rationalized by identification of a functional bromodomain‐like consensus motif in 15‐LOX‐1. This indicates that 15‐LOX‐1 is not only involved in oxidative lipid metabolism, but also in chromatin binding, which suggests a potential role in chromatin modifications. |
format | Online Article Text |
id | pubmed-8518382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85183822021-10-21 Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization Chen, Deng Xiao, Zhangping Guo, Hao Gogishvili, Dea Setroikromo, Rita van der Wouden, Petra E. Dekker, Frank J. Angew Chem Int Ed Engl Research Articles Lipoxygenase (LOX) activity provides oxidative lipid metabolites, which are involved in inflammatory disorders and tumorigenesis. Activity‐based probes to detect the activity of LOX enzymes in their cellular context provide opportunities to explore LOX biology and LOX inhibition. Here, we developed Labelox B as a potent covalent LOX inhibitor for one‐step activity‐based labeling of proteins with LOX activity. Labelox B was used to establish an ELISA‐based assay for affinity capture and antibody‐based detection of specific LOX isoenzymes. Moreover, Labelox B enabled efficient activity‐based labeling of endogenous LOXs in living cells. LOX proved to localize in the nucleus, which was rationalized by identification of a functional bromodomain‐like consensus motif in 15‐LOX‐1. This indicates that 15‐LOX‐1 is not only involved in oxidative lipid metabolism, but also in chromatin binding, which suggests a potential role in chromatin modifications. John Wiley and Sons Inc. 2021-08-31 2021-09-27 /pmc/articles/PMC8518382/ /pubmed/34388301 http://dx.doi.org/10.1002/anie.202106968 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Chen, Deng Xiao, Zhangping Guo, Hao Gogishvili, Dea Setroikromo, Rita van der Wouden, Petra E. Dekker, Frank J. Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title | Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title_full | Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title_fullStr | Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title_full_unstemmed | Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title_short | Identification of a Bromodomain‐like Region in 15‐Lipoxygenase‐1 Explains Its Nuclear Localization |
title_sort | identification of a bromodomain‐like region in 15‐lipoxygenase‐1 explains its nuclear localization |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518382/ https://www.ncbi.nlm.nih.gov/pubmed/34388301 http://dx.doi.org/10.1002/anie.202106968 |
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