Evidence map›Paper›PMID 31500697›Full record

ArticleeLife2019

Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.

Matthew E Cockman, Kerstin Lippl, Ya-Min Tian, Hamish B Pegg, William D Figg, Martine I Abboud, Raphael Heilig, Roman Fischer, Johanna Myllyharju, Christopher J Schofield and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Substrate selectivity and inhibition of the human lysyl hydroxylase JMJD7.Protein science : a publication of the Protein Society · 2024
    Article
  17. Time-resolved NMR detection of prolyl-hydroxylation in intrinsically disordered region of HIF-1α.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Article
  19. Article
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Matthew E Cockman *The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-3310-4821
Kerstin Lippl *Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Ya-Min Tian *Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Hamish B PeggThe Francis Crick Institute, London, United Kingdom.
William D FiggChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-5875-2606
Martine I AbboudChemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-2141-5988
Raphael HeiligTarget Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Roman FischerTarget Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-9715-5951
Johanna Myllyharju *Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.ORCID 0000-0001-7772-1250
Christopher J Schofield *Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-0290-6565
Peter J Ratcliffe *The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-2853-806X
University of Oxford · GBThe Francis Crick Institute · GBUniversity of Oulu · FI

Funding

British Heart Foundation RG/11/1/28684Wellcome Trust FC001501
6 · The paper itself

Abstract

Human 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.

Indexed as

Protein Processing, Post-TranslationalHydroxylationHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesOxygenPeptidesRecombinant ProteinsSubstrate SpecificityEGLN1 protein, humanEGLN2 protein, humanEGLN3 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesOxygenPeptidesRecombinant Proteinsbiochemistrychemical biologyhumanhydroxylationoxygenaseprolyl hydroxylase

Identifiers

PMID31500697
PMCPMC6739866
OpenAlexW2972038063

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.