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eLife 2019;8:e46490, doi: 10.7554/eLife.46490 Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates |
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| Author: | Cockman, Matthew E.1; Lippl, Kerstin2; Tian, Ya-Min3; |
| Organizations: |
1The Francis Crick Institute, London, United Kingdom 2Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom 3Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
4Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
5Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 4 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2020042422333 |
| Language: | English |
| Published: |
eLife Sciences Publications,
2019
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| Publish Date: | 2020-04-24 |
| Description: |
AbstractHuman and other animal cells deploy three closely related dioxygenases (PHD 1, 2 and 3) to signal oxygen levels by catalysing oxygen regulated prolyl hydroxylation of the transcription factor HIF. The discovery of the HIF prolyl-hydroxylase (PHD) enzymes as oxygen sensors raises a key question as to the existence and nature of non-HIF substrates, potentially transducing other biological responses to hypoxia. Over 20 such substrates are reported. We therefore sought to characterise their reactivity with recombinant PHD enzymes. Unexpectedly, we did not detect prolyl-hydroxylase activity on any reported non-HIF protein or peptide, using conditions supporting robust HIF-α hydroxylation. We cannot exclude PHD-catalysed prolyl hydroxylation occurring under conditions other than those we have examined. However, our findings using recombinant enzymes provide no support for the wide range of non-HIF PHD substrates that have been reported. see all
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| Series: |
eLife |
| ISSN: | 2050-084X |
| ISSN-E: | 2050-084X |
| ISSN-L: | 2050-084X |
| Volume: | 8 |
| Article number: | e46490 |
| DOI: | 10.7554/eLife.46490 |
| OADOI: | https://oadoi.org/10.7554/eLife.46490 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
1182 Biochemistry, cell and molecular biology |
| Subjects: | |
| Funding: |
This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001501), the UK Medical Research Council (FC001501), and the Wellcome Trust (FC001501). PJR is also supported by the Ludwig Institute for Cancer Research and the Wellcome Trust (106241/Z/14/Z). CJS, KL, MA, and WDF thank the Wellcome Trust (106244/Z/14/Z), Cancer Research UK, and the British Heart Foundation for funding. KL gratefully acknowledges support via the Newton Abraham D Phil studentship scheme. JM was supported by Academy of Finland project grant 296498, Academy of Finland Center of Excellence 2012–2017 Grant 251314, the S Jusèlius Foundation and the Jane and Aatos Erkko Foundation.
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| Academy of Finland Grant Number: |
296498 251314 |
| Detailed Information: |
296498 (Academy of Finland Funding decision) 251314 (Academy of Finland Funding decision) |
| Copyright information: |
© Cockman et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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https://creativecommons.org/licenses/by/4.0/ |